Bilharzial related, organ confined, muscle invasive bladder cancer: prognostic value of apoptosis markers, proliferation markers, p53, E-cadherin, epidermal growth factor receptor and c-erbB-2

PURPOSE: We investigated the association of the apoptosis related proteins Bcl-2, Bcl-x, Bax and Bak, p53, the adhesion molecule E-cadherin, the receptor proteins epidermal growth factor receptor and c-erbB-2, and the proliferation markers proliferating cell nuclear antigen and Ki-67 with the clinical outcome of bilharzial related transitional cell carcinoma and squamous cell carcinoma. MATERIALS AND METHODS: Cystectomy specimens from 109 patients with organ confined, muscle invasive stage, pT2pN0M0, bilharziall positive bladder cancer were examined, including 60 with squamous cell carcinoma and 49 with transitional cell carcinoma. Immunohistochemical results were correlated with tumor progression. RESULTS: In squamous cell carcinoma but not in transitional cell carcinoma the loss of epidermal growth factor receptor, Bax and Bak was significantly associated with higher histological grade (p = 0.02, 0.006 and 0.01, respectively). On univariate analysis patients with transitional cell carcinoma had a poorer prognosis than those with squamous cell carcinoma. p53 Over expression and the loss of Bak positivity were associated with shortened progression-free survival in transitional cell carcinoma (p = 0.006 and 0.04, respectively), and squamous cell carcinoma (p = 0.00001 and 0.04, respectively). In squamous cell carcinoma high tumor grade (p = 0.02) and in transitional cell carcinoma high labeling indexes for MIB-1, Bcl-x expression and c-erbB-2 positivity (p = 0.03, 0.02 and 0.04, respectively) were associated with a poorer prognosis. On multivariate analysis p53 emerged as a significant prognostic factor for each condition. Additional independent prognostic factors were proliferating cell nuclear antigen for squamous cell carcinoma, and MIB-1, Bcl-x and Bax for transitional cell carcinoma. CONCLUSIONS: Bilharzial related transitional cell carcinoma and squamous cell carcinoma of the bladder differ in interims of protein expression and prognosis. Independent prognostic factors were p53, MIB-1, Bcl-x, and Bax in the former disease, and p53 and proliferating cell nuclear antigen in the latter disease.     

Malignant salivary tumors—analysis of prognostic factors and survival

A group of 113 patients with malignant salivary gland tumors was retrospectively reviewed to analyze the association of clinical and histologic factors with survival. These factors were patient sex and age, tumor site, clinical stage, histologic diagnosis, tumor grade, and whether or not final surgical margins were clear. There were 57 parotid, 40 minor salivary, and 16 submandibular gland cancers. The histologic groups were mucoepidermoid carcinoma (49 patients), adenoid cystic carcinoma (31), adenocarcinoma not otherwise specified (18), acinic cell carcinoma (7), malignant mixed tumor (5), squamous cell carcinoma (2), and undifferentiated carcinoma (1). Univariate analysis of clinical factors showed that age and clinical stage significantly influenced survival. At 10 yr the predicted cumulative survival rates for Stage I, II, III, and IV tumors were 74%, 56%, 32%, and 10%, respectively. Tumor grade was the only significant histologic factor. This was most obviously reflected among patients with mucoepidermoid carcinomas. Cumulative survival at 5 yr was 94% for those with low-grade tumors and 26% for high-grade tumors. By multivariate analysis, clinical stage, age, and tumor grade remained highly significant. Analysis of patients with only Stage I and II disease demonstrated that the significant factors were patient age, tumor site, tumor grade, and whether or not surgical clearance was achieved. These results suggest that clinical stage should not be the exclusive determinant of the extent of surgery and that the selection of patients, for adjuvant therpay may be improved by an awareness of these prognostic factors.     

Malignant salivary tumors--analysis of prognostic factors and survival

A group of 113 patients with malignant salivary gland tumors was retrospectively reviewed to analyze the association of clinical and histologic factors with survival. These factors were patient sex and age, tumor site, clinical stage, histologic diagnosis, tumor grade, and whether or not final surgical margins were clear. There were 57 parotid, 40 minor salivary, and 16 submandibular gland cancers. The histologic groups were mucoepidermoid carcinoma (49 patients), adenoid cystic carcinoma (31), adenocarcinoma not otherwise specified (18), acinic cell carcinoma (7), malignant mixed tumor (5), squamous cell carcinoma (2), and undifferentiated carcinoma (1). Univariate analysis of clinical factors showed that age and clinical stage significantly influenced survival. At 10 yr the predicted cumulative survival rates for Stage I, II, III, and IV tumors were 74%, 56%, 32%, and 10%, respectively. Tumor grade was the only significant histologic factor. This was most obviously reflected among patients with mucoepidermoid carcinomas. Cumulative survival at 5 yr was 94% for those with low-grade tumors and 26% for high-grade tumors. By multivariate analysis, clinical stage, age, and tumor grade remained highly significant. Analysis of patients with only Stage I and II disease demonstrated that the significant factors were patient age, tumor site, tumor grade, and whether or not surgical clearance was achieved. These results suggest that clinical stage should not be the exclusive determinant of the extent of surgery and that the selection of patients, for adjuvant therapy may be improved by an awareness of these prognostic factors.     

Determination of Proliferation Index By MIB-1 Immunostaining in Early Stage Breast Cancer Using Quantitative Image Analysis

Abstract: Several clinicopathologic variables influence prognosis in breast cancer, including stage, histologic grade, nodal status, and tumor size. Multiple studies have shown an independent value of proliferation index as a prognostic variable for the stratification into favorable and unfavorable groups. The monoclonal antibody MIB-1 reacts with the same antigen site, not epitope, as recognized by the Ki-67 antibody. Like Ki-67, MIB-1 reacts with cells in the late G₁, S, M and G₂ phases of the cell cycle, but MIB-1 has the advantage of reacting with formalin-fixed, paraffin-embedded material. The authors investigated the feasibility of using image analysis to quantitate the MIB-1 antibody staining (proliferation index [PI]) and predict survival in a series of 230 patients with stage I and stage II breast cancer. In a univariate Cox regression model, larger values of MIB-1 were related to shorter survival times (p < 0.001). Exploratory statistical procedures were used to categorize the patients into good, intermediate, and poor survival groups using the following proliferation indices as cut-points: <5%, 5–11%, and >11 %, respectively. Higher clinical stage was associated with higher MIB-1 values and shorter survival (p = 0.01, and p = 0.003, respectively). Tumor size (p = 0.02) and nodal status (p = 0.05) were also associated with higher values of MIB-1. After adjusting for age, clinical stage, nodal status, and tumor size in a multivariate analysis, MIB-1 retained its prognostic significance (p < 0.0001) when considered as either a continuous or categorical variable. There were no significant associations between MIB-1 determined proliferation index and age (p = 0.54), histologic grade (p = 0.69), nuclear grade (p = 0.06) or the presence of vascular invasion (p =.66). There is a strong statistical relationship between cell proliferative activity, as determined by MIB-1 expression, and survival in early stage breast cancer.     

Prognostic significance of ploidy, MIB-1 proliferation marker, and p53 in renal cell carcinoma

BACKGROUND: Pathologic stage is currently the best prognostic factor for predicting outcomes in renal cell carcinoma. The objective of this study was to evaluate the role of DNA ploidy, p53, and Ki-67 (MIB-1) as individual and combined prognostic factors for survival in patients with renal cell carcinoma (RCC). STUDY DESIGN: From 1995 to 2004, 117 patients (78 men and 39 women; mean age 57.34 years), undergoing partial (n = 22) or radical (n = 95) nephrectomy for renal cell carcinoma were retrospectively analyzed. Analysis of MIB-1, p53, and DNA ploidy was performed. Disease-free and overall survival was calculated using Cox proportional hazard models. A combined score was given to incorporate p53, MIB-1, and ploidy as a single variable. RESULTS: On univariate analysis, tumor size, nuclear grade, MIB-1 <10% (p = 0.0059), ploidy (p = 0.0124), pathologic stage group, metastasis at time of operation, and combined score (p = 0.0024) were markedly associated with disease-free survival. On multivariate analysis, only metastasis and pathologic stage were pronounced. For overall survival, size, nuclear grade, MIB-1 <10% (p = 0.0167), pathologic stage group, metastasis, and combined score (p = 0.0456) were pronounced on univariate analysis. Only metastasis was pronounced on multivariate analysis. CONCLUSIONS: We incorporated a combined score to evaluate MIB-1, ploidy, and p53 as a single variable. A combined score is able to give a stronger predictive value of the cellular characteristics of each tumor. Individually and combined with p53, MIB-1, and ploidy were of prognostic significance on univariate analysis. Pathologic stage and presence of metastasis remain the best predictors of disease-free survival.     

The role of bcl-2, p53, and ki-67 index in predicting tumor recurrence for low grade superficial transitional cell bladder carcinoma

PURPOSE: We assess the prognostic significance of bcl-2 expression, p53 mutation and ki-67 index for low grade, superficial transitional cell bladder carcinoma. MATERIALS AND METHODS: The medical records of 93 cases of primary, low grade (24 G1, 69 G2), superficial (70 pTa, 23 pT1) transitional cell carcinoma of the bladder were reviewed. Association of bcl-2, p53 and ki-67 index immunoreactivity with tumor grade and stage was examined. Prognostic significance of tumor grade, pathological stage, bcl-2 expression, p53 mutation and ki-67 index in predicting tumor recurrence was assessed. RESULTS: Of the tumors 60 (70%) had p53 mutation and 9 (10.5%) expressed bcl-2. These 2 markers did not relate to tumor grade or pathological stage. Median ki-67 index was 10.9% and positively correlated with tumor grade. Recurrence was noted in 34.9% of patients with a median followup of 26 months (range 1 to 84). The ki-67 index was the only significant prognostic indicator in univariate and multivariate analyses. This marker can further distinguish grade 2 tumors with a favorable prognosis from those with an unfavorable outcome. CONCLUSIONS: The ki-67 labeling index is an independent predictor of tumor recurrence for patients with primary superficial, low grade bladder cancers.     

Correlation of histopathological variants, cellular DNA content, and clinical outcome in adenoid cystic carcinoma of the salivary glands.

OBJECTIVE: To study the correlation between flow cytometrically measured DNA ploidy with prognostically important histopathologic groups and clinical outcome in patients with adenoid cystic carcinoma of the salivary glands. STUDY DESIGN: 46 tumor specimens were analyzed flow cytometrically for DNA content and assessed for histological grade. Correlations were made between tumor DNA ploidy and histopathological grade, and disease-free and overall survival of these patients. RESULTS: Of the 46 patients, 31 had a cribiform/tubular histologic pattern, and 15 had a solid pattern. 84% of the tumors with cribriform/tubular pattern were DNA diploid, compared with 33% of tumors that were graded solid. This difference proved to be statistically significant (chi(2)11.75, P = 0.0006). Overall and disease-free survival periods were longer for patients with DNA diploid tumors in both groups, 63% vs. 36% and 62% vs 38%, respectively. CONCLUSIONS: Tumor DNA ploidy correlates with prognostically important tumor histopathology as well as overall and disease-free survival in patients with adenoid cystic carcinoma of the salivary gland. EBM rating: B-3.     

Polymorphous Low Grade Adenocarcinoma has a Consistent p63+/p40? Immunophenotype that Helps Distinguish it from Adenoid Cystic Carcinoma and Cellular Pleomorphic Adenoma

Polymorphous low grade adenocarcinoma (PLGA) is a tumor of minor salivary glands that exhibits considerable morphologic overlap with adenoid cystic carcinoma and cellular pleomorphic adenoma, especially in small biopsy specimens. Unlike these other tumor types. PLGAs do not harbor a myoepithelial component, yet their frequent positivity for p63 diminishes the usefulness of this particular myoepithelial marker as a discriminating immunostain. p40 is an antibody that recognizes ΔNp63, a p63 isoform that is more specific for true myoepithelial differentiation. As such, p40 immunostaining could help distinguish PLGAs from adenoid cystic carcinomas and pleomorphic adenomas. In this study, p63 and p40 immunohistochemistry was performed on paraffin embedded, formalin fixed tissue from 11 PLGAs, 101 adenoid cystic carcinomas, and 31 pleomorphic adenomas. All 11 PLGAs (100 %) were positive for p63 but completely negative for p40. Among adenoid cystic carcinomas, 91 of 101 (90 %) were positive for p63 and 90/101 (89 %) were positive for p40. The single discordant p63+/p40− adenoid cystic carcinoma exhibited solid architecture and high grade features not typically seen in PLGA. Among pleomorphic adenomas, 21/31 (68 %) were positive for p63 and 13/31 (42 %) were positive for p40. For the pleomorphic adenomas, the discordant p63+/p40− staining pattern was seen only in the overtly mesenchymal chondromyxoid stroma. The cellular epithelial component of the pleomorphic adenomas demonstrated concordant p63+/p40+ or p63−/p40− immunophenotypes. PLGA consistently exhibits a p63+/p40− immunophenotype that can help distinguish it from adenoid cystic carcinoma and cellular pleomorphic adenoma, tumors that characteristically demonstrate concordant p63 and p40 immunostaining patterns. A p63/p40 immunohistochemical panel can provide a valuable tool for making the distinction between these morphologically similar but clinically divergent entities.     

Adenoid cystic carcinoma of the trachea and main-stem bronchus. A clinical, histopathologic, and immunohistochemical study

Twelve cases of adenoid cystic carcinoma of the trachea and main-stem bronchus were histologically analyzed, and the results were examined with reference to the growth pattern of the tumor and the prognosis. The tumors were histologically classified into tubular, cribriform, and solid subtypes. Three histologic grades were established: grade I, tumors with tubular and cribriform subtypes but without solid subtype; grade II, tumors with tubular and cribriform subtypes in which the solid subtype comprised less than 20% of the area; grade III, tumors in which the solid subtype comprised more than 20% of the area. Three gross infiltrating types were established: type I, entirely intraluminal; type II, predominantly intraluminal; type III, predominantly extraluminal. In most cases histologic grade correlated with gross tumor type; that is, grades, I, II, and III were grossly types I, II, and III, respectively. The tumors infiltrating along the tracheobronchial wall were of the tubular or cribriform subtype, but not of the solid subtype. In two patients who died of distant metastasis, the histologic studies revealed the solid subtype. Immunohistochemical analysis demonstrated that the tubular subtype was the most differentiated form and the solid subtype, the most undifferentiated form. The histologic subtype of adenoid cystic carcinoma of the tracheobronchial tree was an important factor in the growth pattern of the tumor and the prognosis.     

S-100 protein in salivary gland tumors: an immunohistochemical study of 129 cases

Immunohistochemical distribution of S-100 protein was evaluated in 129 tumors from major and minor salivary glands. Also, two sensitive immunoperoxidase avidin-biotin methods using either overnight incubation with primary antibody or pretreatment trypsin digestion and half-hour incubation were compared. Tumors with S-100 protein immunoreactivity were demonstrated in numerous benign and malignant histologic categories. Adenoid cystic carcinomas, carcinomas ex pleomorphic adenoma, clear cell carcinomas, and adenocarcinomas NOS showed inconsistent positive staining, whereas all monomorphic and pleomorphic adenomas and polymorphous low grade adenocarcinomas examined stained positively. No staining was observed in mucoepidermoid carcinomas or acinic cell carcinomas. Mesenchymal-like tumor cells with positive immunostaining were seen only in pleomorphic adenomas and trabecular-tubular adenomas. Equivalent results were found with both overnight and same-day digestion techniques. The consistent S-100 protein staining in some histologic tumor categories (pleomorphic and monomorphic adenoma and polymorphous low grade adenocarcinoma) compared to mucoepidermoid carcinoma that is devoid of S-100 protein immunoreactivity has application to some microscopic differential diagnostic situations. Inconsistent staining of adenoid cystic carcinomas and adenocarcinomas did not allow discrimination from other benign and malignant salivary gland tumors with similar histomorphology.     

Adenoid cystic carcinoma (cylindroma) and mucoepidermoid carcinoma of the bronchus. Factors affecting survival.

A review was made of the presentation, treatment, and follow-up of 20 patients with adenoid cystic carcinoma and 12 patients with mucoepidermoid carcinoma of the bronchus who were seen at the Mayo Clinic during the 50 year period 1927 through 1977. Three forms of therapy were employed: complete surgical resection, radiation therapy alone, and radiation therapy after endoscopic removal of tumor tissue. Superior results were obtained in the group with adenoid cystic carcinoma, when complete resection was possible. Significant survival and palliation of sepsis was achieved with subtotal resection. The mucoepidermoid carcinomas in this series were classified on the basis of histologic differentiation. Mucoepidermoid carcinoma of Grade 1 was managed by conservative pulmonary resection. Mucoepidermoid carcinoma of Grades 2 and 3 showed a greater propensity for malignancy. Widespread dissemination caused death with unresectable high-grade mucoepidermoid carcinomas of Grades 2 and 3.     

High Recurrence Rates of Squamous Cell Carcinoma after Mohs'' Surgery in Patients with Chronic Lymphocytic Leukemia

BACKGROUND: Cutaneous cancers exhibit a much higher incidence in patients with chronic lymphocytic leukemia than in nonleukemic patients. Squamous and basal cell carcinomas also exhibit greater subclinical tumor extension in patients with chronic lymphocytic leukemia. OBJECTIVE: The purpose of this study was to estimate and compare the recurrence rates of squamous cell carcinoma after Mohs' surgery in patients with chronic lymphocytic leukemia compared with those in controls and to evaluate differences among squamous cell carcinoma size and histologic grade. METHODS: We retrospectively assessed the clinical histories, postoperative notes, and surgical photographs of patients with chronic lymphocytic leukemia and controls matched (2:1) for age, sex, and surgical year. Both patients and controls underwent Mohs' surgery for squamous cell carcinoma of the head and neck at the Mayo Clinic between March 1988 and April 1999. RESULTS: Twenty-eight patients who underwent Mohs' surgery for 57 squamous cell carcinomas had 7 recurrences. The cumulative incidence of recurrence on a per-tumor basis was 4.3% at 1 year, 14.8% at 3 years, and 19.0% at 5 years. Squamous cell carcinoma was seven times more likely to recur in patients with chronic lymphocytic leukemia than in controls (p = .003). The distribution of tumor histologic grade was not significantly different between patients and controls (p = .39). Maximum preoperative tumor diameters were clinically similar between patients and controls (median 15 mm vs 14 mm; p = .04). CONCLUSION: The recurrence rates of squamous cell carcinoma were significantly higher in patients with chronic lymphocytic leukemia. Squamous cell carcinomas in patients with chronic lymphocytic leukemia did not exhibit a significant difference in histologic grade or clinical difference in preoperative tumor size. Close surveillance for squamous cell carcinoma recurrence is warranted in patients with chronic lymphocytic leukemia.     

Clinical features and immunoexpression of p53, MIB-1 and proliferating cell nuclear antigen in adrenal neoplasms

PURPOSE: We evaluated the clinical features and immunoreactivity of p53 protein, MIB-1 antigen and proliferating cell nuclear antigen (PCNA) in adrenal neoplasms. MATERIALS AND METHODS: A total of 26 patients with adrenocortical adenoma and 24 patients with carcinoma were treated with adrenalectomy. Clinical features and immunohistochemical reactions were compared in adult vs pediatric tumors. RESULTS: There was a bimodal age distribution of carcinomas and adenomas, with a first peak occurring before age 5 years. The proportion of carcinomas in children (18 of 29) was higher than in adults (6 of 21). Carcinoma and adenoma occurring in children presented more commonly as the virilizing syndrome, while in adults Cushing's syndrome was more common. All adenomas in adults were p53 negative, while in children 4 of 11 adenomas (36%) were p53 positive. Histological Weiss criteria were the most reliable pathological features to distinguish adenoma from carcinoma. Other pathological features, including tumor weight, rate of mitotic figures and immunoexpression of p53 protein, MIB-1 antigen and PCNA, exhibited a striking difference in adenomas and carcinomas but none demonstrated sensitivity or specificity of 100%. Of all the computerized tomographic characteristics analyzed, including tumor size, shape, necrosis/hemorrhage, attenuation and contrast enhancement, only tumor size (greater than 5 cm) showed sensitivity and specificity of 100% in the differential diagnosis. Children and adults with carcinoma had similar curves of survival (p = 0.76). Carcinoma stage and PCNA immunoexpression displayed an association with outcome. CONCLUSIONS: Endocrine syndromes differed in adults and children but other clinical features were similar in both groups. The role of p53 protein, MIB-1 antigen and proliferating cell nuclear antigen in discrimination of adenomas from carcinomas is unclear.     

p53, bcl-2, and Bax Expression in Renal Cell Carcinoma

Objectives. Renal cell carcinomas often show a high degree of resistance to chemotherapy and radiation despite expressing normal function of the protein p53. The loss of control of apoptosis may also contribute to progression and resistance to treatment modalities and can be attributed to an interaction between p53 and the apoptotic regulators bcl-2 and Bax. To determine whether the expression of p53, bcl-2, or Bax could be correlated with outcome, we analyzed the expression pattern of these proteins in renal cell tumor samples.Methods. We examined 28 patients with clear cell renal cell carcinomas along with 7 patients with papillary renal cell carcinomas and 4 with renal oncocytomas. All renal cell carcinomas were clinically localized Stage pT2 with tumor size ranging from 4.0 to 10.3 cm (mean 6.23). Immunohistochemistry was performed on all samples and correlated with markers of outcome, including tumor grade, metastasis, recurrence, and overall survival rate.Results. In all clear cell tumors, the detection level of p53 expression was below the sensitivity of the assay, consistent with the reported infrequent incidence of p53 mutations in renal cell cancers. bcl-2 expression showed a significant correlation (P = 0.018) with higher tumor grade but could not be significantly correlated with other parameters examined including tumor recurrence, metastasis, or survival rate. The expression of Bax could similarly be correlated with higher tumor grade but with none of the other parameters.Conclusions. At the present time, the combination of both tumor grade and stage represents the best prognostic markers available. Adjunctive use of bcl-2 and Bax staining currently plays a minimal role in helping to further stratify patients at high risk for disease progression or recurrence.     

Sarcomatoid differentiation in renal cell carcinoma: a study of 101 cases

Sarcomatoid renal cell carcinoma is not a distinct histologic entity and represents high-grade transformation in different subtypes of renal cell carcinoma. It is not known whether any particular histologic type has a predilection for sarcomatoid change or whether the primary histologic type of renal carcinoma undergoing sarcomatoid change affects prognosis. Of 952 consecutively histologically subtyped renal cell carcinomas, the incidence of sarcomatoid differentiation was 8% in conventional (clear cell) renal carcinoma, 3% in papillary renal carcinoma, 9% in chromophobe renal carcinoma, 29% in collecting duct carcinoma, and 11% in unclassified renal cell carcinoma. One hundred one renal cell carcinomas with sarcomatoid change were studied, and clinicopathologic parameters were correlated with outcome. The mean age of patients was 60 years (range, 33-80 years), and the male-to-female ratio was 1.6:1. The median tumor size was 9.2 cm (range, 3-25 cm). The primary histologic subtype of the carcinoma component was conventional (clear cell) renal carcinoma in 80 cases, papillary renal carcinoma in eight, chromophobe renal carcinoma in seven, collecting duct carcinoma in two, and unclassified renal cell carcinoma in four. The sarcomatoid component resembled fibrosarcoma in 54 cases, malignant fibrous histiocytoma in 44, undifferentiated sarcoma (not otherwise specified) in three with focal rhabdomyosarcomatous component in two of them. The spindled elements accounted for 1% to 99% of the sampled tumor (median, 40%; mean 45%). The histologic grade of the spindled elements was intermediate to high in 92 cases and low in nine cases. Most cases were TNM stages III and IV (seven stage I, six stage II, 63 stage III, and 25 stage IV). Follow-up was available in 88 patients; 61 (69%) patients died of disease and had a median survival time of 19 months. Distant metastases, most frequently to the lungs, were documented in 51 (66%) of 77 patients who had available clinical information regarding distant metastasis. The disease-specific survival rate was 22% and 13% after 5 and 10 years, respectively, compared with a cohort of renal cell carcinomas without sarcomatoid change with a 5-and 10-year disease-specific survival of 79% and 76%, respectively. Kaplan-Meier survival analysis showed that tumors with high TNM stage (p = 0.0027), at least 50% sarcomatoid component (p = 0.0453), and angiolymphatic invasion (p = 0.0282) were associated with decreased survival rates. The primary histologic subtype of the carcinoma component and the type and grade of the sarcomatoid component did not affect survival. In a Cox proportional hazard regression model, TNM stage appeared to be the only significant variable in predicting outcome among renal cell carcinomas with sarcomatoid change (p = 0.018; risk ratio, 6.984 and 8.439). Compared with a cohort of renal cell carcinomas without sarcomatoid change, sarcomatoid tumors tended to present at a more advanced stage (p = 0.0001). Also, when adjusted for stage, necrosis, and tumor size, patients with tumors with sarcomatoid differentiation had a worse prognosis than did patients with tumors without sarcomatoid change (p = 0.0001). In conclusion, sarcomatoid change in renal cell carcinoma portends a worse prognosis. Because tumors with even a small component of sarcomatoid change may have an adverse outcome, this finding, when present, should be noted in the surgical pathology report.     

Basaloid squamous carcinoma of the anal canal with an adenoid cystic pattern: histologic and immunohistochemical reappraisal of an unusual variant

Two cases of a distinctive variety of basaloid squamous carcinoma (BSC) of the anal canal are described. Both occurred in female patients who presented with bleeding per rectum. Histologic evaluation of the tumors showed lobules and aggregates of medium-sized basaloid cells with distinctive peripheral palisading and focal areas of central, comedo-necrosis. Accompanying dysplasia of the overlying squamous mucosa was absent. However, the microscopic pattern was dominated by the presence of eosinophilic, hyaline, paucicellular basement membrane-like material around and within tumor nests. This appearance together with microcystic spaces simulated that of an adenoid cystic carcinoma. Immunohistochemistry of the tumors revealed the following profile: CK7, CK5/CK6, 34betaE12 positive, CK14 focally positive but CK20 negative. The following were all negative: EMA, CEA, smooth muscle and muscle-specific actin, calponin, and S-100. The tumor cells exhibited diffuse nuclear positivity with p63. The eosinophilic basement membrane hyaline material was positive for collagen type IV and also for laminin. BSC of the anal canal with an adenoid cystic pattern is an infrequently encountered and reported variant, although it is seen more often in the aerodigestive tract. There may be an increased propensity for BSC with an adenoid cystic pattern to metastasize to the liver, but the number of cases encountered are too small to be definitive. The histologic differential diagnosis is true salivary gland-type adenoid cystic carcinoma and basal cell adenocarcinoma. Immunohistochemistry and awareness of this unusual pattern of BSC will facilitate the correct diagnosis being reached.     

肾细胞癌中bcl-2、p53、增殖细胞核抗原表达与细胞增殖和凋亡

目的 探讨肾细胞癌(RCC)中bcl—2、p53、增殖细胞核抗原(PCNA)表达与细胞增殖、凋亡及病理参数之间的关系。方法 应用链霉亲和素辣根过氧化物酶(SABC)法分析34例RCC标本中bcl—2、p53和PCNA蛋白的表达，应用末端脱氧核苷酸转移酶介导的脱氧三磷酸尿苷苦(dUTP)缺口末端标记(TUNEL)法检测细胞凋亡。结果 34例RCC标本中，15(44．1％)例bcl-2阳性表达，表达阳性率与增殖指数(PI)、凋亡指数(AI）及RCC病理学参数无关；仅有3例p53表达阳性；PI为6．0％--24．0％(平均为12．3％)，AI为2．0％--8．0％(平均为5．4％)；PI与肿瘤分级、分期密切关系，AI与肿瘤分级有明显关系。结论 明显增高的PI和AI与肿瘤恶性表型有关，提示在RCC中肿瘤细胞过度增殖伴有频繁的凋亡发生。     

Contemporary staging and prognosis for primary tracheal malignancies: a population-based analysis.

OBJECTIVE: Determine staging characteristics and survival outcomes for primary malignancies of the trachea. Design Cross-sectional analysis of national cancer database. METHODS: Cases of primary tracheal malignancy were extracted from the Surveillance, Epidemiology, and End Results database for the time period 1988-2000. T-stage, N-stage, and overall stage of presentation were determined. Mean, median, and 5-year survival statistics were computed using Kaplan-Meier survival analysis for each tumor histology and for the overall cohort according to stage. RESULTS: Ninety-two cases with adequate histologic information were identified. Mean age at presentation was 59.3 years with an equal sex distribution. Squamous cell carcinoma was the most common tumor type (41 cases) followed by adenoid cystic carcinoma (19 cases). Forty-nine cases (53%) presented with stage 3 or stage 4 disease. Squamous cell carcinoma exhibited poorer survival (mean survival, 44.0 month, 5-year survival, 34%) than adenoid cystic carcinoma (mean survival, 115 month, 5-year survival, 78%). Five-year unadjusted survival rates according to overall stage were 52.8%, 70.0%, 75.0%, 15.1%, respectively. CONCLUSIONS: Primary tracheal malignancies often present with advanced stage. Patients with squamous cell carcinoma of the trachea have poorer prognoses when compared with adenoid cystic carcinoma and other tumor types. Staging tracheal cancer with a TNM-based system helps predict survival. EBM rating: C.     

Cell membrane and cytoplasmic staining for MIB-1 in hyalinizing trabecular adenoma of the thyroid gland

The monoclonal MIB-1 antibody reacts with the nuclei of cells in the late G1, S, G2, and M phases of the cell cycle. Previously, we found two cases of hyalinizing trabecular adenoma that showed cell membrane and cytoplasmic immunopositivity for the antibody. The purpose of this investigation was to confirm this exceptional reactive pattern of MIB-1 in hyalinizing trabecular adenoma. For the study, we collected 13 additional hyalinizing trabecular adenomas and stained a total of 15 tumors using MIB-1 antibody. Ten cases of papillary thyroid carcinoma were studied similarly. All hyalinizing trabecular adenomas showed strong positivity for the antibody in 90% or more of the tumor cells, localized especially to the cell membrane and also to the cytoplasm. There was no cell membrane or cytoplasmic MIB-1 positivity among the 10 papillary carcinomas. Luminal border of normal extratumoral thyroid follicles rarely showed faint immunopositivity. Our findings indicate that strong cell membrane and cytoplasmic immunoreactivity for MIB-1 is a characteristic of the hyalinizing trabecular adenoma. Staining for MIB-1 will be useful in differentiating hyalinizing trabecular adenoma from papillary carcinoma, which shares a number of cytologic and histologic findings with hyalinizing trabecular adenoma.     

Apoptosis in Ductal Carcinoma in Situ of the Breast

Abstract: Programmed cell death (apoptosis) may play a role in tumor development and progression. The importance of apoptosis dysregulations in ductal carcinoma in situ (DCIS) and its relationships with p53 mutations and expression of bcl-2 has received little attention in the literature. In a series of 58 DCIS patients, we evaluated the number of apoptotic cells by the TUNEL technique in subgroups of DCIS and correlated it with immunohistochemical expression of hormone receptors, c- erb B-2, p53, bcl-2, and Ki-67 (MIB-1) and DNA content measured by image cytometry. High apoptotic index (greater than 3%) was related to high tumor grade, negative hormone receptors, c- erb B-2 overexpression, aneuploidy and lack of bcl-2 immunohistochemical stain. Apoptosis was not related to p53 or proliferative index. The findings are similar to those found in infiltrating breast cancer.