The behavior of endometrial hyperplasia. A long-term study of "untreated" hyperplasia in 170 patients

Endometrial curettings from 170 patients with all grades of endometrial hyperplasia, who did not undergo a hysterectomy for at least 1 year were evaluated in order to correlate the histopathologic features with behavior. Follow-up ranged from 1 to 26.7 years (mean, 13.4 years). Cytologic and architectural alterations were analyzed separately in order to assess their respective roles in predicting the likelihood of progression to carcinoma. Classification of proliferative lesions based solely on the presence of cytologic atypia revealed that atypia was a discriminant factor. Proliferations lacking cytologic atypia were designated hyperplasia and those displaying atypia were designated atypical hyperplasia. Only 2 (1.6%) of 122 patients with hyperplasia progressed to carcinoma compared with 11 (23%) of women with atypical hyperplasia (P = 0.001). Subclassification of the two forms of hyperplasia (those with cytologic atypia and those without) was performed using the degree of architectural abnormalities. Hyperplasia and atypical hyperplasia displaying marked glandular complexity and crowding producing a back-to-back appearance were designated complex hyperplasia (CH) and complex atypical hyperplasia (CAH), respectively. Hyperplasia and atypical hyperplasia with lesser degrees of glandular complexity and crowding were designated simple hyperplasia (SH) and simple atypical hyperplasia (SAH), respectively. Progression to carcinoma occurred in 1 (1%) of 93 patients with SH, in 1 (3%) of 29 patients with CH, in 1 (8%) of the patients with SAH, and in 10 (29%) of the patients with CAH. The differences between the four subgroups suggest a trend but are not statistically significant. The findings in this study provide a rationale for classifying noninvasive endometrial proliferations primarily on the basis of cytologic atypia since this is the most useful criterion in predicting the likelihood of progression to carcinoma. In addition, the presence of concommitant architectural alterations appears to identify a particularly high-risk subgroup.     

The prognostic significance of p53, p27 kip1, p21 waf1, HER-2/neu, and Ki67 proteins expression in gastric cancer: a clinicopathological and immunohistochemical study of 121 Arab patients

BACKGROUND: The variability of prognosis within a pathological stage of gastric cancer (GC) at presentation, underscores the need for specific biological markers to identify subgroups of patients with aggressive course for intensive treatment. To our knowledge, this is the first study from an Arab population reporting on the relationship of p53, p27 kip1, p21 waf1, HER-2/neu, and Ki67 expression, and clinicopathological features and their prognostic significance. METHODS: Formalin-fixed paraffin-embedded tumors were studied by immunohistochemistry, using monoclonal antibodies to p53, p27 kip1, p21 waf1, HER-2/neu, and Ki67. The results were correlated with clinicopathological features and survival. RESULTS: M:F = 80:41; median age = 60 years; stage III and IV = 71%; and median follow-up = 34.4 months. Positive expression rates of p53, p27 kip1, p21 waf1, Ki67, and HER-2/neu were 54%, 40%, 8.3%, 70%, and 12% respectively. p53 expression correlated with age <60 years (P = 0.03), tumor size >5 cm (P = 0.01), p27 kip1 and Ki67 expression (P = 0.0001), and HER-2/neu (P = 0.04). p21 waf1 correlated inversely with T-stage (P = 0.008) and Her-2/neu expression correlated with histological grade (P = 0.04) and T-stage (P = 0.008). Univariate analysis showed that p53 overexpression (P = 0.01), fungating and infiltrative macroscopic appearance (P = 0.02), size >5 cm (P = 0.0001), lymph node metastasis (P = 0.0001), p T3 and T4 disease (P = 0.01), and overall stage III and IV (P = 0.0001) disease were adverse prognostic factors. Patients with tumor profiles p53 (-)/p27 (+) had better survival than those with p53 (+)/p27 kip1 (-)(P = 0.02). On multivariate analysis by Cox regression model, the expression of p53 (P = 0.03) and lymph node involvement (P = 0.01) were significant adverse prognostic factors for overall survival. CONCLUSIONS: The expression of p53 in Arab patients with GC correlates with aggressive tumor characteristics and is an independent prognostic factor. The combined analysis of p53 and p27 kip1 is of added prognostic value.     

Young age as an independent adverse prognostic factor in premenopausal patients with breast cancer

Breast cancer in younger patients appears to be more aggressive than disease occurring in older patients. Even though large population-based studies suggest poorer survival of patients younger than 35 years, data demonstrating the relationship of age and prognosis within premenopausal cohorts are much more scarce and conflicting. In this retrospective analysis of 885 premenopausal patients, the relationship between age, typical prognostic factors, treatment, and patient outcome was investigated. Eight hundred four patients (90.8%) > 35 years and 81 patients (9.2%) = 35 years who had been treated for stage I/II breast cancer were evaluated. Median follow-up time was 71 months. The prevalence of adverse prognostic features such as tumor size, tumor type, tumor grading, pathologic lymph node status, and hormone receptor status were evenly distributed between the two age groups. Age = 35 years proved to be a powerful independent prognostic factor in multivariate analyses of recurrence-free (P < 0.0001; relative risk [RR] = 2.5) and overall survival (P < 0.0039, RR = 2.2). Thus, in the face of evenly distributed risk factors in this strictly premenopausal, homogeneous population, young age was seen as the second most powerful risk factor after lymph node status. According to these findings, patients diagnosed with breast cancer at = 35 years of age have a worse prognosis compared to premenopausal women above this age. Future studies should focus on unveiling the young age surrogate in order to improve treatment and prognosis.     

胃肠道间质瘤预后多因素分析

目的探讨胃肠道间质瘤的相关预后因素。方法复阅切片,重新诊断,从肿瘤的两点取材,构建组织微阵列。以免疫组织化学染色检测CD117、CD34、SMA、Desmin及S-100 5种蛋白的表达,分析各临床病理变量与预后的关系。结果194例患者1,3,5年生存率分别为93．5％、72．1％和63．2％;单因素分析显示,患者的预后与肿瘤大小、核分裂相数目、肿瘤坏死、肿瘤部位、肿瘤细胞密集程度、肿瘤细胞类型、核异型性、出血、手术方式、周围脏器组织有无侵犯、黏膜有无受侵、性别等因素有关（P〈0．05）;多因素分析显示,周围组织肿瘤侵犯、肿瘤坏死、肿瘤大小、核分裂相数目及性别是影响预后的重要因素。结论肿瘤大小及核分裂相数目是影响预后的重要因素,但准确判别预后尚应结合肿瘤坏死、性别、肿瘤部位及其他病理参数进行。     

儿童颅内原发性非生殖细胞瘤性生殖细胞肿瘤疗效分析

目的 探讨儿童颅内原发性非生殖细胞瘤性生殖细胞肿瘤（NGGCT）的临床特征,及其预后影响因素。方法 回顾性分析2008年11月至2019年6月在本中心接受放疗的40例NGGCT患儿的临床资料,90%患儿接受全脑全脊髓放疗,所有患儿接受铂类为基础的化疗。采用Kaplan‐Meier曲线分析生存情况,采用log‐rank检验分析预后相关因素。结果 原发部位以松果体、鞍区/鞍上、基底节为主;中位发病年龄为108个月（20~204个月）;中位随访时间33个月（8~131个月）,3、5年总生存率均为82.0%;3、5年无进展生存率分别为78.6%和73.0%。单因素分析发现甲胎蛋白（AFP）升高（P=0.02）,初诊年龄>10岁（P=0.006）,初诊时有转移（P<0.001）,肿瘤病理学类型中含有绒毛膜癌、卵黄囊瘤和/或胚胎性癌成分（P=0.036）是患儿独立的不良预后因素。结论 患儿AFP升高、初诊年龄>10岁、肿瘤转移播散、病理类型是儿童颅内NGGCT独立的不良预后因素。其整体预后差于生殖细胞瘤,需要多学科合作强化治疗以提高生存。     

儿童颅内原发性非生殖细胞瘤性生殖细胞肿瘤疗效分析北大核心CSCD

目的探讨儿童颅内原发性非生殖细胞瘤性生殖细胞肿瘤(NGGCT)的临床特征,及其预后影响因素。方法回顾性分析2008年11月至2019年6月在本中心接受放疗的40例NGGCT患儿的临床资料,90%患儿接受全脑全脊髓放疗,所有患儿接受铂类为基础的化疗。采用Kaplan-Meier曲线分析生存情况,采用log-rank检验分析预后相关因素。结果原发部位以松果体、鞍区/鞍上、基底节为主;中位发病年龄为108个月(20~204个月);中位随访时间33个月(8~131个月),3、5年总生存率均为82.0%;3、5年无进展生存率分别为78.6%和73.0%。单因素分析发现甲胎蛋白(AFP)升高(P=0.02),初诊年龄>10岁(P=0.006),初诊时有转移(P<0.001),肿瘤病理学类型中含有绒毛膜癌、卵黄囊瘤和/或胚胎性癌成分(P=0.036)是患儿独立的不良预后因素。结论患儿AFP升高、初诊年龄>10岁、肿瘤转移播散、病理类型是儿童颅内NGGCT独立的不良预后因素。其整体预后差于生殖细胞瘤,需要多学科合作强化治疗以提高生存。     

Therapeutic strategy for patients with pN0 gastric carcinoma

BACKGROUND AND OBJECTIVES: The prognosis for patients with pN0 gastric cancer is moderately hopeful (expected 5-year survival: 80%). However, the relevant prognostic factors and most appropriate surveillance protocol have not been identified. METHODS: We investigated 733 gastric cancer patients without lymph node metastasis for prognostic factors by uni- and multi-variate analysis and by documenting causes of death and recurrence patterns. RESULTS: Univariate analysis revealed that age, tumor location, macroscopic appearance, tumor diameter, invasion depth, lymphatic invasion, and venous invasion affected prognosis. Multivariate analysis showed that age (> or = 60 years), ill-defined macroscopic appearance, and undifferentiated histological type independently reduced survival rates. Age (> or = 60 years) and undifferentiated histological type adversely influenced prognosis in 507 early gastric cancer patients whereas ill-defined macroscopic appearance adversely affected prognosis in 226 advanced cancer patients. Recurrence patterns in these patients were similar to those produced by lymph node metastasis. The predominant recurrence pattern was peritoneal dissemination, observed 2-3 years post-resection. CONCLUSIONS: This study identified adverse prognostic factors in pN0 gastric cancer patients. Randomized controlled studies of adjuvant chemotherapy are necessary to assess whether such therapy is beneficial for patients with adverse prognostic factors.     

Prognostic assessment of gastrointestinal stromal tumor

The term "gastrointestinal stromal tumor" (GIST) has been applied to a collection of distinctive mesenchymal tumors occurring within the human gastrointestinal tract. As new drug therapy becomes available, data regarding the natural history of these unusual tumors are necessary to provide selection factors for treatment. Ninety-eight patients had light microscopy compatible with GIST at a single institution from 1989 to 2000. After immunostaining with c-kit and histopathologic review, 69 were judged to be GIST. All prognostic indicators were determined for gastric GIST, intestinal GIST, and all locations combined. The location of the GIST did not have a significant impact on survival. Clinically, tumor size, peritoneal cancer index, and completeness of cytoreduction had a significant impact on prognosis for GIST at all locations. Pathologically, cytologic atypia, necrosis, invasion and number of mitoses were significant prognostic indicators for GIST. Criteria to separate three pathologic groups of GIST according to the tumor size and the mitotic count were useful to evaluate the tumor behavior; in the borderline pathologic group invasion and cytologic atypia were statistically significant prognostic criteria. The cell phenotypes, as determined by immunostains, correlated with the prognosis of gastric GIST but not intestinal GIST. A correlation between the immunostain Ki-67 but not CD-34 or desmin and the prognosis was observed. It is possible to select clinical and pathologic parameters of GIST that impact on prognosis. Invasion and necrosis help to determine the prognosis with borderline tumors. The immunostain Ki-67 correlated with the prognosis and may be helpful to assess prognosis when dealing with small biopsy specimens.     

Peritoneal washing cytologic analysis of ovarian serous tumors of low malignant potential to detect peritoneal implants and predict clinical outcome

BACKGROUND:

Patients with ovarian serous tumors of low malignant potential (OSLMP) who have peritoneal implants, especially invasive implants, are at an increased risk of developing tumor recurrence. To the best of the authors' knowledge, the ability of peritoneal washing (PW) cytology to detect the presence and type of peritoneal implants has not been adequately investigated, and its prognostic significance is unknown.

METHODS:

Records and PW specimens of 101 patients diagnosed with and treated for OSLMP between 1996 and 2010 at The University of Texas MD Anderson Cancer Center were retrospectively reviewed. Patients' staging biopsy findings were compared with the results of the authors' review of the PWs. Follow‐up data were also analyzed.

RESULTS:

Of the 96 patients for whom staging biopsy results were available, 26 (27%) had peritoneal implants (17 noninvasive and 9 invasive), 19 (20%) had endosalpingiosis, and 51 (53%) had negative findings. The PW specimens of 18 of the 26 patients (69%) with peritoneal implants were positive for serous neoplasm, and a correlation was found between cytologic and histologic findings (P < .0001). The sensitivity, specificity, positive predictive value, and negative predictive value were 69%, 84%, 62%, and 88%, respectively. Four of 101 patients had disease recurrence; 3 of these patients had invasive implants and 1 patient had noninvasive implants. None of the patients who had negative staging biopsy findings or endosalpingiosis but did have PW specimens that were positive for serous neoplasm developed disease recurrence.

CONCLUSIONS:

PW cytology detects the presence of peritoneal implants with moderate accuracy. However, long‐term studies are needed to determine whether positive PW cytologic findings are an independent predictor of tumor recurrence. Cancer (Cancer Cytopathol) 2012;. © 2012 American Cancer Society.     

IL28RA在胃癌组织中的表达及其与临床病理特征和预后的关系

目的:分析胃癌组织中IL-28RA的表达情况,以及与患者临床病理特征和预后的关系。方法:对胃癌组织芯片进行IL28RA、CD8及PD-L1免疫组化染色并判读。采用χ²检验分析IL28RA蛋白表达与胃癌患者临床病理特征的关系。采用Kaplan-Meier生存分析进行预后单因素分析,使用COX回归进行多因素分析。结果:共纳入94例胃癌患者,平均年龄62.4岁,其中男性55例,病理分级1-2级患者39例,肿瘤最大直径≤5 cm的54例,83%患者肿瘤发生于胃体及胃窦(78/94),Ⅲ-Ⅳ期患者56例。我们发现癌与癌旁组织IL28RA表达无统计学差异。将IL28RA评分>3及≤3分为高表达及低表达组,结果显示IL28RA表达在肿瘤TNM分期及PD-L1表达情况存在差异(P<0.05),而与性别、年龄、肿瘤部位、大小等方面无差异。IL28RA高表达的胃癌患者预后更好(P=0.01)。多因素分析显示TNM分期、CD8⁺T细胞比例和IL28RA表达水平是影响胃癌预后的独立预测因素,HR分别为1.39(P=0.04)、0.55(P=0.04)和0...     

Clear cell sarcoma of tendons and aponeuroses: a study of 75 patients

BACKGROUND: Clear cell sarcoma (CCS) of tendons and aponeuroses (malignant melanoma of soft parts) is a rare melanocytic soft tissue sarcoma. The objective of this study was to determine the clinical features, prognostic factors, and optimal treatment policy for patients with this rare disease. METHODS: Seventy-five consecutive patients with histologically confirmed CCS who received treatment between 1980 and 2004 were analyzed retrospectively. RESULTS: There were 41 men and 34 women, and the median age was 36 years. Sixty-five tumors were located in the extremities, and 10 tumors were located in the trunk. The median tumor size was 4 cm. Seventy-one patients underwent surgical excision, and 56 patients received chemotherapy. Sixteen patients developed local recurrences, and 52 patients developed metastasis. The overall patient survival rates was 47% at 5 years and 36% at 10 years. Univariate analysis showed that sex (P = .018), tumor size (P = .001), tumor depth (P = .002), TNM classification (P = .001), and surgical margin (P = .042) were significant prognostic factors. Among the 52 patients who presented with localized disease, sex (P = .023), tumor size (P = .002), tumor depth (P = .011), TNM classification (P = .004), and chemotherapy (P = .032) were identified as significant prognostic factors. Multivariate analysis showed that tumor size remained an independent prognostic factor in both groups. CONCLUSIONS: The current results supported the contention that early diagnosis and initial wide excision are essential for a favorable outcome of CCS. The role of chemotherapy for CCS should be investigated further.     

Stage I-II follicular lymphoma. Treatment results for 76 patients

Clinical features and treatment results are analyzed for 76 patients with Stage I-II follicular lymphoma seen between 1974 and 1981. During this period, 66% of the patients received involved-field radiotherapy (XRT) alone, and 34% received chemotherapy with or without XRT. At 5 years, the overall survival was 67%, the cause-specific survival was 73%, and the relapse-free survival (RFS) was 48%, with no relapses to date among nine patients followed beyond 60 months. Adverse prognostic features for survival included extranodal disease and elevated serum lactate dehydrogenase. For RFS, adverse features included extranodal disease and bulky abdominal disease. The RFS was significantly better for patients receiving chemotherapy with or without XRT than for XRT alone (64% versus 37% at 5 years, P = 0.02), despite a higher frequency of adverse prognostic features in the chemotherapy-treated group. About 50% of Stage I-II follicular lymphoma patients may be curable, and the inclusion of chemotherapy in the initial treatment may increase the potentially curable fraction.     

Prognostic significance of histologic grading compared with subclassification of papillary thyroid carcinoma

BACKGROUND: Papillary thyroid carcinomas represent a diversity of morphologic subtypes and variants, but to the authors' knowledge the prognostic significance of subclassification is not clear. Therefore, the authors compared the value of histologic classification with a combined assessment of histologic key features such as marked nuclear atypia, tumor necrosis, and vascular invasion (i.e., histologic grade). METHODS: One hundred twenty-eight surgically treated patients with papillary carcinoma > 10 mm were studied. The tumors were subclassified and individual histologic features were examined and compared in univariate and multivariate survival analyses. RESULTS: Of all the cases, 55% were of the usual type, whereas 27% showed complex histologic features with different components present and 18% represented specific subtypes. Tall cell differentiation showed an increased frequency of tumor necrosis and vascular invasion, and tumors with solid areas had an increased occurrence of mitotic figures and vascular invasion. Patients with tall cell tumors tended to have reduced survival (P = 0.074), and two patients with columnar cell features died of the disease. When combined, the group of patients with all tumor subtypes had significantly reduced survival when compared with the remainder of patients (P = 0.034), although the difference was only minor. Histologic grade was highly significant (P = 0.0001) in survival analysis, together with mitotic frequency (P = 0.028), S-phase (P = 0.015), and G(2)M-phase fractions (P = 0.040). In multivariate analysis, tumor dimension (P = 0.019) and histologic grade (P = 0. 008) showed significant and independent prognostic importance, whereas subclassification was not found to be significant. CONCLUSIONS: Subclassification of papillary thyroid carcinomas had only a minor prognostic impact, whereas histologic grade was a strong and independent prognostic marker. The authors recommend that all papillary carcinomas be given a histologic grade based on a combined examination of nuclear atypia, tumor necrosis, and vascular invasion. [See editorial on pages 1766-68, this issue.] Copyright 2000 American Cancer Society.     

Blastic natural killer cell lymphoma/leukemia (CD56-positive blastic tumor): prognostication and categorization according to anatomic sites of involvement

BACKGROUND: Blastic natural killer (NK) cell lymphoma/leukemia (BNKL) is an immature CD56-positive neoplasm, which was recognized recently and characterized by systemic proliferation of tumor cells including skin, lymph node, and bone marrow. METHODS: The current study analyzed 47 patients with BNKL (27 had leukemias and 20 had lymphomas). Patient data were collected for the survey of the NK-Cell Tumor Study Group. RESULTS: There were 33 males and 14 females, with a median age of 53 years (range, 3 months to 89 years). There were few clinicopathologic differences between the leukemia and lymphoma types. Cutaneous involvement was noted at diagnosis in 28 patients, who presented a tendency for older age of onset (median: 56 vs. 46 years, P = 0.11) than patients with noncutaneous BNKL. Cutaneous BNKL showed less frequent mediastinal involvement (4% vs. 53%, P = 0.0002) and less severe thrombocytopenia (P =0 .03). Phenotypic characteristics were also different, with cutaneous BNKL favoring CD4 and HLA-DR expression, and noncutaneous BNKL favoring CD16 and CD34 expression. Both groups responded well to chemotherapy for lymphoid malignancies, but disease recurrence was frequent. The prognosis of patients with noncutaneous BNKL was significantly poorer than that of patients with cutaneous BNKL (median survival: 15 vs. 25 months, P = 0.02). Multivariate analysis confirmed that cutaneous involvement was a significant and independent prognostic factor for BNKL, as were age of onset and leukocyte count. CONCLUSIONS: These findings suggested that BNKL is a heterogeneous disease and contains at least two subtypes. Although further investigations are needed to settle a marker for distinction, the presence of cutaneous involvement is a useful prognostic factor.     

185例肝细胞癌临床病理学分析

目的 探讨肝细胞癌(HCC)的临床病理特征与预后的关系.方法 收集185例行手术切除并获得随访的HCC患者的临床资料,男性169例(91.4%),女性16例(8.6%),男女比例为10.6∶1;年龄19～72岁,平均年龄(51.0±11.0)岁.采用Kaplan-Meier法和Cox风险回归模型分析HCC患者临床病理特征与预后的关系.结果 全组患者的术后3年和5年生存率分别为52.0%和38.0%.Kaplan-Meier单因素分析结果显示,肿瘤数目(P=0.000)、肿瘤大小(P=0.025)、组织学结构类型(P=0.000)、核分级(P=0.000)、分化程度(P=0.001)及血管浸润(P=0.000)均与HCC患者的预后明显相关.组织学结构类型中,细梁状型、致密梁状型和假腺样型患者的生存时间差异无统计学意义(P＞0.05),但明显高于粗梁状型、实性型和硬化型(P＜0.05),硬化型患者的生存时间与实性型的差异无统计学意义(P＞0.05),但明显短于其余各型(P＜0.05).核分级为1级与2级患者的生存时间差异无统计学意义(P＞0.05),3级与4级患者的生存时间差异无统计学意义(P＞0.05),但3级患者的生存时间明显短于1、2级(P＜0.05).Cox风险回归模型分析结果显示,肿瘤数目(P=0.001)、肿瘤大小(P=0.042)、核分级(P=0.023)和血管浸润情况(P=0.000)是影响HCC患者预后的主要因素.结论 肿瘤数目、肿瘤大小、核分级和血管浸润情况是影响HCC患者预后的主要因素,肿瘤数目越多、肿瘤越大、核分级越高和有血管浸润者的死亡风险越大.     

The significance of atypia within teratomatous metastases after chemotherapy for malignant germ cell tumors

The completely resected teratomatous metastases of 55 patients who had been treated with cisplatin-based combination chemotherapy for non-seminomatous germ cell tumors were reviewed to see if cellular atypia had an effect with respect to recurrent disease. The degree of atypia of the epithelial and mesenchymal elements was assessed on the basis of the cytologic features and mitotic activity. Twenty-three percent of the cases contained high-grade epithelial elements, whereas high-grade mesenchymal elements occurred in 18% of the cases; in addition there were nine cases classified as showing frankly malignant teratomatous elements. The presence of cytologically disturbing epithelial and mesenchymal elements (which, however, lacked an invasive malignant pattern) correlated with an increased incidence of recurrent teratoma compared to less atypical teratomatous elements (23% vs. 6% for epithelial elements, and 18% vs. 9% for mesenchymal elements, respectively). This difference, however, was not statistically significant (P greater than 0.05). There was no correlation between teratomatous atypia and recurrent, non-teratomatous germ cell tumor. The presence of an invasive malignant pattern did identify patients at significantly increased risk for recurrent teratoma-derived tumor. The authors conclude that cytologic atypia in the absence of invasion is not sufficient justification for altering the usual therapeutic strategies for patients with teratomatous metastases.     

c-erbB-2 (HER-2/neu) gene amplification is a better indicator of poor prognosis than protein over-expression in operable breast-cancer patients

Our aim was to compare the prognostic value of c-erbB-2 gene amplification analyzed by Southern blot with that of protein (p185) over-expression measured by immunohistochemistry in 172 patients with operable breast cancer (BC). Amplification and p185 over-expression were found in 31 (18%) and 51 (30%) BCs, respectively. All but 1 of the tumors showed both amplification and over-expression, while 21 (12%) tumors displayed over-expression without amplification. The risk of death associated with c-erbB-2 gene amplification and p185 over-expression was evaluated by multivariate analysis, taking into account tumor size, histoprognostic grade, hormone receptors and axillary node status. During a mean follow-up of 9.5 (+/-2) years, node involvement (p < 0.001), c-erbB-2 gene amplification (p = 0.02) and negative hormone receptors (p = 0.02) were found to be independent prognostic indicators of the risk of death. Over-expression of p185 with no amplification was not correlated with this risk. When the risk of death associated with c-erbB-2 amplification was studied according to chemo- and hormone therapy, no significant difference was observed between subgroups of subjects. Amplification was also associated (p = 0.02) with the risk of multifocal distant metastases (i.e., metastases detected concomitantly in at least 2 sites) and, thus, with BC aggressiveness. These data show the importance of c-erbB-2 gene amplification in predicting the long-term outcome of patients and in selecting eligible patients for c-erbB-2-targeted therapies.     

Apoptotic and mitotic indices predict survival rates in lymph node-negative colon carcinomas.

An imbalance between apoptosis and mitosis is believed to underlie colon cancer development and progression. These processes regulate the growth of normal and neoplastic epithelia, and in tumors, may confer prognostic information. To test this hypothesis, we determined apoptotic and mitotic indices (AI, MI) by morphology in H&E sections of 154 lymph node-negative, sporadic colon carcinomas. The relationship of these indices to genetic (p53 and Bcl-2) and biological features (DNA ploidy and cell kinetics) and patient survival rates was determined. Tumor features were compared in proximal and distal tumors, given postulated differences in their pathogenesis. Bcl-2 and p53 proteins were examined using immunohistochemistry and DNA ploidy and proliferative indices (PIs) by flow cytometry. Tumor features were dichotomized for analysis of relapse-free survival and overall survival (OS) rates using a Cox proportional hazards model. Median patient follow-up was 8.8 years. The median AI and MI were 1.2% (0-7.6) and 0.40% (0-1.8), respectively, and did not differ by tumor site. AI correlated with histological grade (P = 0.03); MI correlated with PI (P = 0.02) and inversely with Bcl-2 in distal tumors (P = 0.02). p53 and Bcl-2 expression were detected in 52 and 53% of tumors, respectively. Distal tumor site was associated with aneuploidy (P = 0.001), p53 (P = 0.001), and PI > 15% (P = 0.002). In a univariate analysis, colon cancers with high MIs (>0.5%) had a poor prognosis (P = 0.04). Bcl-2 overexpression (>20% + tumor cells) was associated with more favorable OS (P = 0.04). The association of ploidy and PI with outcome was of borderline significance for all tumors; however, diploidy predicted better survival in proximal cancers. In distal cancers, low AIs (< or = 0.25%) and high MIs (>0.5%) were adverse prognostic markers. After adjustment for other variables, an increased MI predicted shorter OS with a hazard ratio (HR) for death of 2.70; 95% confidence interval (CI) was 1.23-5.91 (P = 0.01). Expression of Bcl-2 was associated with more favorable OS (HR, 0.46; 95% CI, 0.21-1.0; P = 0.06). In proximal cancers, Bcl-2 expression was the most important predictor of OS (HR, 0.17; 95% CI, 0.03-0.85; P = 0.03). In distal tumors, low AIs (HR, 3.33; 95% CI, 1.27-9.09; P = 0.01) and high MIs predicted poor survival. In conclusion, increased mitosis and low or absent Bcl-2 expression are significant risk factors for death in node-negative colon cancers, as are low rates of apoptosis in distal tumors. If validated prospectively, our results may identify patient subsets than can benefit from adjuvant chemotherapy.     

Outcomes after conservative treatment of advanced-stage serous borderline tumors of the ovary

BackgroundThe aim of this study was to assess the outcomes of the largest series of patients treated conservatively for a stage II or III serous borderline ovarian tumor.Materials and methodsFrom 1969 to 2006, 41 patients were treated conservatively for an advanced-stage serous borderline ovarian tumor. Patient outcomes were reviewed.ResultsTwenty patients had undergone a unilateral salpingo-oophorectomy, 18 a unilateral cystectomy and two bilateral cystectomy (unknown for one patient). Three patients had invasive implants. The median duration of follow-up was 57 months (range 4–235). The recurrence rate was high (56%), but overall survival remained excellent (100% at 5 years, 92% at 10 years). One death had occurred due to an invasive ovarian recurrence. Eighteen pregnancies (nine spontaneous) were observed in 14 patients.ConclusionsThis study demonstrates that spontaneous pregnancies can be achieved after conservative treatment of advanced-stage borderline ovarian tumors (with noninvasive implants) but the recurrence rate is high. Nevertheless, this high rate has no impact on survival. Conservative surgery can be proposed to patients with a borderline tumor of the ovary and noninvasive peritoneal implants. Should infertility persist following treatment of the borderline tumor, an in vitro fertilization procedure can be cautiously proposed.     

Serum parathyroid hormone-related peptide is associated with systemic inflammation and adverse prognosis in gastroesophageal carcinoma

BACKGROUND: Parathyroid hormone-related peptide (PTHrP) is a tumor-derived circulating factor that has been associated with hypercalcemia of malignancy. The role of PTHrP as a prognostic indicator remains unclear. Studies suggest that it may function as a growth factor; and, recently, the ability of PTHrP to induce cytokine expression has been described. PTHrP also has been proposed as a procachectic factor. In this study, the authors investigated the prognostic value of PTHrP in patients who had gastroesophageal carcinoma without hypercalcemia and determined whether PTHrP was associated with systemic inflammation and adverse nutritional status. METHODS: Patients were recruited at the time of diagnosis. Serum was collected for determination of c-terminal fragment PTHrP (cPTHrP) levels (by radioimmunoassay) and calcium levels as well as levels of serum cytokines and acute-phase proteins (with an enzyme-linked immunosorbent assay). Nutritional assessment of patients was undertaken at the same time as serum collection. Patients underwent routine staging, and survival duration was recorded. RESULTS: One hundred fifty-one patients with esophagogastric carcinoma were recruited. Six of 151 patients (4.0%) patients were hypercalcemic, and 26 patients (17.2%) had elevated serum cPTHrP levels. There was no association between the cPTHrP level and either serum calcium concentrations (P = 0.72) or adverse nutritional status. Elevated cPTHrP, however, was associated with significantly higher serum levels of soluble tumor necrosis factor receptor (P = 0.008) and with significantly lower levels of transferrin (P = 0.009) and albumin (P = 0.02). There was also a weak association with C-related protein levels (P = 0.06). Elevated cPTHrP levels also were associated with an adverse prognosis, as determined by reduced survival duration, on univariate analysis (P = 0.038), but not on multivariate analysis (P = 0.15). CONCLUSIONS: Elevated serum cPTHrP levels were present in approximately 17% of patients with gastroesophageal carcinoma in the absence of hypercalcemia and was associated with markers of systemic inflammation and with an adverse prognosis.