Clinical significance of A, B, H isoantigen deletion of urothelial cells in bladder carcinoma

The occurrence and/or deletion of A, B, H isoantigens in cytologic specimens was compared to a number of other clinical parameters commonly used for prediction of prognosis or monitoring of bladder carcinoma. Isoantigens were better preserved by our preparation for cytologic than for histologic specimens. Patients with isoantigen present on urothelial cells were more likely to have small or no visible tumors than large tumors. A strong correlation was found between isoantigen status and cytologic diagnosis (P less than 0.001), but not with ploidy (P = 0.059). For short-term prognosis of recurrence, tumor size appeared to be highly significant, whereas A, B, H isoantigen determinations had no predictive value. Intravesical chemotherapy did not per se influence expression/deletion of isoantigens.     

Predictive survival markers in patients with surgically resected non-small cell lung carcinoma.

Among patients with resected non-small cell lung carcinoma, about 50% will present a tumor recurrence. Thus, it would be of major importance to be able to predict and try to prevent these relapses by an active chemotherapy and/or radiotherapy. In an attempt to answer this question, the tumors of 227 patients with a surgically resected non-small cell lung carcinoma were evaluated as follows: tumors were classified as squamous cell carcinoma (n = 132) or adenocarcinoma (n = 95), and tumor differentiation was evaluated for each type. Then, all tumors were classified in respect to their pathological TNM staging (WHO) and screened by immunohistochemistry for the detection of the expression of the following antigens: Bcl-2, A+B+H blood group antigens, c-erb-b2, p53, and Pan-Ras antigens. Furthermore, adenocarcinomas were screened for the presence of point mutations in Ki-Ras codons 1-31. Finally, the patient blood group was defined, and patient survival was analyzed using nonparametric tests and proportional hazard Cox models. Using Kaplan-Meier survival curves, disease pathological TNM staging was shown to be a strong predictive factor of survival for both squamous cell carcinoma and adenocarcinoma. Patients with squamous cell carcinoma experienced fewer relapses than those with adenocarcinoma (42% versus 63%; P = 0.0002) and had a significantly better survival. All evaluated antigens were more often present in squamous cell carcinoma than in adenocarcinoma except for Pan-Ras (three times more frequent in adenocarcinoma). In patients with squamous cell carcinoma, only tumor staging had a significant prognosis value (P = 0.01). In patients with lung adenocarcinoma, a well-differentiated tumor (P = 0.009) as well as a positive Bcl-2 staining (P = 0.009) and an A+B+H antigen tumor staining (P = 0.024) were associated with a better survival. In contrast, patients with a stage I or II disease and a p53-positive tumor staining and patients with the O blood group (P = 0.01) had a shorter survival. Interestingly, no relation with patient survival was related to c-erb-b2 and Pan-Ras staining. Finally, 12 point mutations were found out of 81 tumors (15%) evaluated for Ki-Ras codons 1-31; they involved codon 12 but also 8, 14, and 15 without any relationship to survival. In respect to lung adenocarcinoma, using Cox proportional hazard models stratified on tumor staging, the following markers were shown to be related to survival: (a) Independent markers of longer survival (ie., high histological degree of tumor differentiation and positive Bcl-2 and A+B+H blood group antigen expression by tumor cells); and (b) Independent markers of shorter survival (i.e., O blood group for all patients and p53 tumor staining in patients with stage I and II diseases). This study suggests that, in patients who undergo surgery for lung adenocarcinoma, the presence or absence of these criteria could be used to define a subset of patients who may benefit from a more specific follow-up.     

ABO(H) antigens and beta-2 microglobulin in transitional cell carcinoma. Predictors of response to intravesical bacillus Calmette-Guerin.

The response of patients with superficial transitional cell carcinoma of the bladder (STCB) to intravesical chemotherapy is variable; some patients enjoy a long period without recurrence, whereas others have recurrence of tumor within 2 years of removal of the primary lesion. Previously, others have demonstrated that the loss of normal cell surface antigens, such as ABO(H) blood group antigens or beta-2 microglobulin (B2M) has been correlated with more aggressive behavior by tumor. In this study, using immunohistochemical techniques, the authors evaluated the initial pretreatment biopsy specimen of bladder tumors for the presence of ABO(H) antigens and B2M. Data from this sample patient population, all with biopsy-proven STCB, indicate that expression of these two markers is predictive of a therapeutic response to prophylactic intravesical bacillus Calmette-Guerin (BCG) (Tice strain) after resection, and that expression of the two markers is of greater predictive value than expression of either antigen alone.     

Prognostic factors in survival of bladder cancer.

Clinical and pathologic data of 36 patients with transitional cell carcinoma of the bladder were investigated to determine the significance on patient survival of these factors: pathologic grade and stage; the immunohistochemistry of eight cell and tumor markers; nuclear DNA flow cytometric parameters; and patient smoking status. The bivariate and multivariate statistical analysis significantly correlated patient survival rates with the immunohistochemical expression of blood group, isoantigens A (P less than 0.05), O(H) (P = 0.001), the oncogene-related protein ORP-p21 (P less than 0.05), the pathologic grade and stage (P = 0.002), and the tumor DNA ploidy (P less than 0.05). Smoking status correlated aneuploidy (P less than 0.05) and tumor expression of ORP-p21 (P less than 0.05) with the patient survival rate. Despite the relatively small number of patients in this study, the results suggest that the clinicopathologic variables are significant factors in survival of bladder cancer.     

原发性肺癌患者血清中相关肿瘤标志物表达水平的变化及其临床意义

目的探讨肿瘤标志物[癌抗原125、CY211、癌胚抗原、鳞状细胞癌抗原(SCC)及神经原特异性烯醇化酶(NSE)]在原发性肺癌患者血清中的变化情况及意义。方法选取肺癌患者50例(甲组)、肺良性疾病患者50例(乙组)及健康人群50例作为研究对象,并采用化学发光法检测3组肿瘤标志物表达水平。结果甲、乙组各项肿瘤标志物水平明显高于健康人群组,差异具有统计学意义,P<0.05。甲组患者癌胚抗原(CEA)及CY211(cytokeratin-19-fragment,CY211)水平明显高于乙组(P<0.05)。与临床手术组织病理检查结果比较,小细胞肺癌患者神经原特异性烯醇化酶(neuron specific enolase,NSE)阳性率较其他类型肺癌高,而腺癌患者中癌抗原125(CA125)阳性率最高,鳞癌患者中CY211阳性率表达最高,P<0.05。结论检测肿瘤标志物,尤其是血清CEA、CY211,有助于肺癌诊断;同时检测不同肿瘤标志物还有利于肺癌的临床病理分型,从而可为临床治疗提供指导价值。     

Altered antigen expression predicts outcome in squamous cell carcinoma of the head and neck

Monoclonal antibody UM-A9 identifies an antigen found on the basal surface of epithelial cells and expressed on all of the squamous cell carcinomas (SCC) that we have tested. In a previous study, we showed that cell lines from metastatic or recurrent SCC exhibit stronger expression of the A9 cell membrane antigen than cell lines from the primary tumor of the same donors, suggesting that this marker is associated with tumor progression. Loss of expression in tumor tissue of normal A, B, and H (ABH) blood group antigens has also been linked to clinical behavior in some epithelial cancers. To determine the prognostic significance of these antigen markers, we prospectively evaluated tissue specimens for expression of these markers in a group of 82 consecutive, previously untreated patients with SCC of the head and neck. Three patterns corresponding to strong (pattern 1), intermediate (pattern 2), or weak (pattern 3) A9 antigen expression were observed. Fifty-eight percent of the patients whose tumors had pattern 1 A9 antigen expression and 78% of the patients with loss of blood group antigen had early relapse, compared with only 34% of those with A9 antigen pattern 2 or 3 (P = .042) and 37% of those whose tumors expressed the mature ABH blood group antigen (P = .012). The combination of A9 pattern and ABH blood group antigen expression in tumor tissue was the variable most strongly associated with duration of disease-free survival, even after adjustment for the traditional prognostic factors of tumor site, stage, and TNM classification. Loss of blood group was the most significant single variable associated with early recurrence, but among patients whose tumors retained ABH blood group antigen expression, the A9 pattern distinguished good and poor prognostic groups. To our knowledge, our study is the first to demonstrate that differences in blood group antigen expression are significantly correlated with disease-free survival in SCC of the head and neck. We have initiated a study (a) to determine the relationship of the A9 antigen and the blood group antigens with clinical response of the tumors and (b) to determine whether these markers should be used as prognostic indicators.     

Pretreatment serum levels of cytokines and cytokine receptors in patients with non-small cell lung cancer, and correlations with clinicopathological features and prognosis. M-CSF - an independent prognostic factor

OBJECTIVES: Cytokines are potential new serum markers, especially desirable for malignancies with poor prognosis like non-small cell lung cancer (NSCLC). METHODS: Cytokines, tumor necrosis factor alpha (TNFalpha), interleukin (IL)-6 and IL-8, soluble TNF (sTNF) RI, sTNF RII, soluble IL-2 receptor-alpha, IL-1 receptor antagonist (IL-1ra), IL-10, vascular endothelial growth factor, basic fibroblast growth factor, and macrophage (M-CSF) and granulocyte colony-stimulating factor, as well as tumor markers - carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC) and CYFRA 21.1 - were assessed in the sera of 103 untreated NSCLC patients, and these cytokines and tumor markers were referred to clinical parameters of the disease and to the overall survival of patients evaluated during a 6-year follow-up. RESULTS: Most of the factors analyzed were found to be elevated in the sera of NSCLC patients, and increases in IL-6, IL-8 and sTNF RI were noted in the greatest proportion of stage I patients. Most cytokine/cytokine receptor levels revealed higher sensitivity than the standard tumor markers; IL-6 and IL-1ra levels were significantly different in patients with squamous cell versus adenocarcinoma; IL-6 and IL-10 were related to the tumor size, while IL-6 and M-CSF levels significantly increased with disease progression. A significant prognostic value of pretreatment serum M-CSF and CEA levels in NSCLC patients has been shown, but only M-CSF proved to be an independent prognostic factor. CONCLUSIONS: Increased pretreatment serum M-CSF level is a significant independent predictor of poor survival in patients with NSCLC.     

Clinical significance of the number of positive tumor markers in assisting the diagnosis of lung cancer with multiple tumor marker assay

The clinical significance of multiple tumor marker assay in assisting the diagnosis of lung cancer was assessed in 67 patients with primary lung cancer, and 115 with nonmalignant pulmonary disease. The tumor markers studied were carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), squamous cell carcinoma-related antigen (SCC), and tissue polypeptide antigen (TPA). The positive rates for all of the tumor markers were significantly higher in the lung cancer group than in the nonmalignant pulmonary disease group. The sensitivity was 31-66%, the specificity was more than 90% for all five markers, and the accuracy was 69-82%. Among the markers, the positive rate of CEA was best correlated with adenocarcinoma (Ad), NSE with small cell carcinoma (Sm), SCC with squamous cell carcinoma (Sq), CA19-9 with Ad, and TPA with Ad. In multiple tumor marker assay, as the number of combined markers was increased, the sensitivity of the assay became higher and the specificity became lower, resulting in a lower accuracy. However, when more than two markers were positive, the relative possibility of lung cancer was increased 90-100%. The number of positive tumor markers in multiple tumor marker assay indicated that it would be of auxiliary value for the diagnosis of lung cancer.     

Prognostic value of histopathologic parameters in squamous cell carcinoma of the oropharynx

Seventy-seven patients with squamous cell carcinoma of the oropharynx were treated by preoperative radiation therapy (4000-5000 rad) followed by surgical resection. The original biopsy specimens were evaluated for degree of keratinization, nuclear pleomorphism, frequency of mitoses, inflammatory response, vascular invasion, and pattern of invasion. Multivariant analysis (Cox regression model) and life table survival function were used to determine the relative contributions of the clinical and histologic parameters to patient outcome. The results were as follows: (1) large tumor size, nodal metastases, and male sex were found to be predictive of a poorer survival (P = 0.004, 0.0167, and 0.0237, respectively); and (2) an analysis of a combination of clinical and histologic parameters demonstrated that the pattern of invasion was the only histologic factor that was predictive of survival (P = 0.0436). Neoplasms invading as large cohesive aggregates indicated a better prognosis than neoplasms invading as thin, irregular cords or individual cells. Restricting the statistical evaluation to only histologic factors (excluding clinical factors) demonstrated that increased frequency of mitoses also correlated with poor survival (P = 0.0218). Further restriction of the analysis to T2 and T3 neoplasms that have similar survival times indicated that both frequency of mitoses and pattern of invasion were of prognostic value in predicting survival (P = 0.0127 and 0.0168, respectively).     

Tissue isoantigens A,B, and H in carcinoma of the cervix uteri: Their clinical significance

A specific red cell adhesion test was done in 243 patients with carcinoma of the cervix uteri and showed the presence of isoantigens in only 27.16% of the patients with infiltrating squamous cell carcinoma. There was a gradual loss of isoantigens during the development of carcinoma. The test can be usefully employed in studying the evolution of the disease. The negativity of the test was found to increase as clinical severity of the disease increases. Also, the highest percentage (57.57%) of retained isoantigen was found in large-cell nonkeratinizing carcinoma, a well-differentiated type for the cervix. Follow-up studies suggest that the loss of antigen indicates probable metastasis and a poor prognosis.     

Tumor markers in uterine cancers

In diagnosing uterine cancers, cells and tissue samples can be directly obtained from the lesion. Cytologic and histologic investigation is the best method for screening and early detection of primary uterine cancers. Tumor markers may be useful for monitoring the clinical course of therapy and early detection of recurrence for which cytologic examination can not be done. Moreover, high levels of tumor markers may represent tumor invasiveness and metastasis to lymph nodes and/or other organs, and may indicate a poor prognosis for the patient. Strictly speaking, tumor markers are not tumor-specific but tumor-associated substances. They can be elevated in sera from healthy individuals under various conditions, and from patients with benign tumors. Squamous cell carcinoma-associated antigen (SCC) is relatively tumor-specific, and widely used for monitoring patients with squamous cell carcinoma not only of the uterine cervix. On the other hand, there is no specific tumor marker for uterine corpus carcinoma. Combination assay of several tumor markers including cancer antigen 125 (CA125) as a core marker may be of greater diagnostic value in cases of uterine corpus carcinoma.     

Stereologic, histopathologic, flow cytometric, and clinical parameters in the prognostic evaluation of 74 patients with intraoral squamous cell carcinomas.

BACKGROUND AND METHODS. A consecutive series of all 78 incident cases of intraoral squamous cell carcinoma occurring during a 2-year period in a population of 1.4 million inhabitants were evaluated by histologic score (the modified classification of Jacobsson et al.), flow cytometry, stereology, tumor size, and the TNM classification. RESULTS. The investigation showed a significant difference between the volume-weighted mean nuclear volume (nuclear vv) of oral leukoplakia (n = 29) and oral squamous cell carcinomas (P = 0.001). The value of the parameters as prognostic indicators of survival and recurrence was tested with Kaplan-Meier plots and Cox multiple hazard regression analysis. Tumor size, T-stage, stereologically estimated nuclear vv, and mean nuclear profile area were all of significant prognostic value in single factor analysis with reference to both survival and recurrence. The histologic parameters of mitotic activity, morphologic nuclear dedifferentiation, and histologic mean malignancy score and the DNA ploidy level had no prognostic value. A prognostic index based on the results of the Cox analysis that included T-stage and nuclear vv was correlated highly with survival (P = 0.00001) and recurrence (P = 0.002). CONCLUSION. These findings may contribute to optimal and individualized therapy.     

A,B and H isoantigens in oral lesions

Expression of blood group A, B and H iso-antigens in oral mucosae was demonstrated by specific red cell adherence test in forty seven mucosal biopsies from oral cavity (14 normal, 10 leucoplakia and 23 squamous cell carcinomas). All normal mucosae gave a positive reaction whereas in malignancy only 6 cases of well differentiated squamous cell carcinomas were either weekly positive or showed a patchy reaction. Remaining cases were negative irrespective of their grading. In leucoplakia though the test was positive in all the cases, the intensity of adherence was less as compared to normal mucosa. The intensity of adherence was found to be directly related to the degree of cellular differentiation. Study of A, B and H isoantigens might help in deciding the prognosis in leukoplakia and/or early detection of malignancy.     

肺癌细胞的HLA抗原表达与组织类型及免疫修饰

目的 了解肺癌细胞的ＨＬＡ抗原表达及肺癌的组织类型和免疫饰对其的影响。方法 采用免疫组织化学方法和流式细胞术从体探讨肺癌组织的ＨＬＡ－ＤＲ抗原表达。结果 在５６例病理确诊的肺癌患者癌组织中,腺癌７６％（２３／２９）,鳞癌８％（２／２４）表达为ＨＬＡ－ＤＲ抗原阳性,而３例小细胞癌均为阴性。腺癌的阳必同于鳞癌和小细胞癌（Ｐ〈０．０５）。ＨＡＬ－ＤＲ抗原阳性癌细胞周围可见较多的淋巴细胞浸润,二者呈明显的     

术前平均血小板体积预测老年食管鳞癌患者术后生存情况的价值

目的:探讨术前平均血小板体积(MPV)预测老年食管鳞癌患者术后生存情况的价值。方法:纳入2014年1月-2016年12月在我院接受手术治疗的259例老年食管鳞癌患者作为研究对象,绘制术前MPV预测老年食管鳞癌患者术后生存情况的ROC曲线，获得术前MPV的最佳诊断截点，根据术前MPV的最佳诊断截点将所有患者分为两组，Logistic模型估计每个患者的倾向性评分，运用1∶1最近邻居倾向性匹配评分(PSM)法将两组中的倾向性评分最为相近的两个患者进行配对，比较匹配前后两组间各临床病理指标的均衡性，Kaplan-Meier生存分析比较匹配后两组患者术后无病生存率和总生存率，Cox回归模型进行敏感性分析，验证匹配后术前MPV对老年食管鳞癌术后生存情况的预测价值。结果:259例老年食管鳞癌患者术后1年、3年、5年无病生存率和总生存率分别为60.3%、41.9%、25.1%和86.1%、62.6%、43.2%，ROC分析结果显示，术前MVP预测老年食管鳞状细胞癌患者术后生存情况的AUC 为 0.835(95%CI:0.776~0.897)，最佳诊断截点为12.7 fL，相应的灵敏度和特异度分别为83.6%和85.4%，根据术前MPV的最佳诊断截点，将所有患者分别分为MPV≥12.7 fL组112例(43.2%)和MPV<12.7 fL组147例(56.8%)，采用1∶1最近邻居 PSM法，结果两组共65对匹配成功，匹配后两组肿瘤直径、胸膜粘连、TNM/T分期、淋巴结转移、淋巴结转移数目、脉管癌栓6个指标比较均无明显差异，两组间各指标分布的均衡性得到了明显的提高(P>0.05)，Kaplan-Meier生存分析显示，匹配后MPV≥12.7 fL组患者术后1年、3年、5年无病生存率明显低于MPV<12.7 fL组(51.6%、23.8%、18.5% vs 66.5%、48.8%、32.7%，χ2/P=5.789/0.024)，MPV≥12.7 fL组患者术后1年、3年、5年总生存率明显低于MPV<12.7 fL组(85.6%、51.8%、32.5% vs 92.5%、72.8%、51.7%，χ2/P=5.674/0.026)，Cox回归分析显示，老年食管鳞癌患者术前MVP每增加1 fL，患者术后5年内肿瘤复发转移的风险增加0.895倍，患者术后5年内死亡的风险增加1.016倍。结论:MPV作为活化血小板的评价指标可用于评估老年食管鳞癌患者术后的生存情况，并且具有较高的预测价值。     

Discrimination of Cancer Stem Cell Markers ALDH1A1, BCL11B,BMI-1, and CD44 in Different Tissues of HNSCC Patients

Cancer stem cells (CSCs) are accountable for the progress of head and neck squamous cell carcinoma (HNSCC). This exploratory study evaluated the expression of molecular CSC markers in different tissues of HNSCC patients. Tissue specimens of primary tumor, lymph node metastases and macroscopically healthy mucosa of 12 consecutive HNSCC patients, that were treated with surgery and adjuvant radio(chemo)therapy upon indication, were collected. Samples were assessed for the expression of p16 as a surrogate for HPV-related disease and different molecular stem cell markers (ALDH1A1, BCL11B, BMI-1, and CD44). In the cohort, seven patients had HPV-related HNSCC; six thereof were oropharyngeal squamous cell carcinoma. While expression of BMI-1 and BCL11B was significantly lower in healthy mucosa than both tumor and lymph node metastasis, there were no differences between tumor and lymph node metastasis. In the HPV-positive sub-cohort, these differences remained significant for BMI-1. However, no significant differences in these three tissues were found for ALDH1A1 and CD44. In conclusion, this exploratory study shows that CSC markers BMI-1 and BCL11B discriminate between healthy and cancerous tissue, whereas ALDH1A1 and CD44 were expressed to a comparable extent in healthy mucosa and cancerous tissues.     

Loss of p63 and cytokeratin 5/6 expression is associated with more aggressive tumors in endometrial carcinoma patients

p63 and cytokeratin (CK) 5/6 are markers of basal and squamous differentiation in several normal epithelia and human tumors and are also suggested to be markers of progenitor or stem cells in certain stratified epithelia. In endometrial carcinoma, there is very limited information about the expression pattern of p63 or CK5/6 and no prognostic information. The aim of our study was to examine whether the expression of these markers was associated with a certain tumor phenotype in terms of other biomarkers, clinicopathologic characteristics and patient prognosis. Immunohistochemical expression of p63 and CK5/6 was examined using tissue microarrays (TMAs) in a large population-based series of 276 endometrial carcinomas with long and complete follow-up. Selected cases of normal and hyperplastic endometrium were examined for comparison (n = 15). Absence of p63 expression (70%) was significantly associated with nonendometrioid carcinomas, high histologic grade (FIGO), higher mitotic count and tumor cell proliferation by Ki-67, microsatellite instability (MSI) and loss of hMSH6 expression. A tendency toward reduced patient survival was also seen (p = 0.098). Presence of CK5/6 expression was more frequent in endometrioid tumors with squamous differentiation, while loss of CK5/6 expression (54%) was significantly associated with high FIGO stage, reduced beta-catenin expression, MSI and reduced patient survival (p = 0.0001); the latter was also found within the endometrioid subgroup (p = 0.0004). Multivariate survival analysis revealed that loss of CK5/6 expression had an independent prognostic impact in addition to well-known prognostic variables. Expression of both markers was increased in simple hyperplasia compared with normal endometrium. In complex hyperplasia, p63 expression was also increased, whereas CK5/6 was positive in areas with squamous differentiation only. Thus, loss of p63 or CK5/6 was associated with features of aggressive tumors, and lack of CK5/6 was significantly associated with reduced survival in multivariate analysis.     

Traditional and newer pathologic factors.

There has long been a pressing clinical need to identify prognostic and predictive factors for patients with breast cancer. Although numerous candidate biological and molecular markers have been identified during the last two decades, traditional factors such as lymph node status, tumor size, histologic type, histologic grade, and hormone receptor status remain the most useful indicators of prognosis and therapeutic response. A major obstacle to the translation of research advances into clinically useful prognostic and predictive markers has been the considerable methodologic variability used in the evaluation of the newer markers. It is now generally accepted that, to be useful in patient management, a putative prognostic or predictive marker must have clinical importance, independence, significance, and standardization with regard to methods, interpretation, and reporting. It is hoped that recognition and adoption of these criteria will serve to clarify the value of newer biologic and molecular markers.     

The levels of expression of galectin-1, galectin-3, and the Thomsen-Friedenreich antigen and their binding sites decrease as clinical aggressiveness increases in head and neck cancers

BACKGROUND: The aim of this study was to investigate whether an increase in malignancy level is accompanied by significant modifications of the expression of galectin-1, galectin-3, and Thomsen-Friedenreich antigen (T antigen) as well as the expression of binding sites for these three markers in head and neck squamous cell carcinomas (HNSCCs). METHODS: Immunohistochemical and glycohistochemical staining reactions were carried out with antibodies, labeled lectins, and a custom-made neoglycoprotein on the basis of histologic slides from a retrospective series of 40 normal and 75 HNSCC formalin fixed, paraffin embedded tissues, and were quantitatively described with the aid of computer-assisted microscopy. RESULTS: Whatever the histologic type, the epithelial tissues in HNSCC exhibited very significantly (P < 0.01 to P < 0. 0001) lower amounts of galectin-1, galectin-3, and T antigen and their respective binding sites than their corresponding normal counterparts. The tumors of the larynx differed very significantly (P < 0.0001 to P < 0.000001) from all the other tumor types. A loss of differentiation in the HNSCCs is accompanied first by the loss of expression of galectin-3 and galectin-3-reactive sites and then by that of the T antigen and its binding site(s). The opposite feature was observed when the parameters associated with the TNM classification were taken into account. The negative lymph node HNSCCs could be distinguished (P = 0.02) from the positive lymph node HNSCCs on the basis of a loss of galectin-3 expression. The modifications occurring in the extent of expression of galectin-1 and galectin-1-reactive sites were relatively marginal in comparison with those observed for galectin-3-dependent and T- antigen-dependent staining. CONCLUSIONS: The decrease in the extent of expression of galectin-3 and galectin-3-reactive sites, T antigen and T antigen-binding sites, and, to a lesser extent, galectin-1 and galectin-1-reactive sites correlates significantly with an increasing level of clinically detectable HNSCC aggressiveness.     

A multimarker model to predict outcome in tamoxifen-treated breast cancer patients.

PURPOSE: This study was designed to produce a model to predict outcome in tamoxifen-treated breast cancer patients based on clinicopathologic features and multiple molecular markers. EXPERIMENTAL DESIGN: This was a retrospective study of 324 stage I to III female breast cancer patients treated with tamoxifen for whom standard clinicopathologic data and tumor tissue microarrays were available. Nine molecular markers were studied by semiquantitative immunohistochemistry and/or fluorescence in situ hybridization. Cox proportional hazards analysis was used to determine the contributions of each variable to disease-specific and overall survival, and machine learning was used to produce a model to predict patient outcome. RESULTS: On a univariate basis, the following features were significantly associated with worse survival: high pathologic tumor or nodal class, histologic grade, epidermal growth factor receptor, ERBB2, MYC, or TP53; absent estrogen receptor (ER) or progesterone receptor; and low BCL2. CCND1 and CDKN1B did not reach statistical significance. On a multivariate basis, nodal class, ER, and MYC were statistically significant as independent factors for survival. However, the benefit of ER-positive status was moderated by BCL2, ERBB2, and progesterone receptor. BCL2 and TP53 also interacted as an independent risk factor. A kernel partial least squares polynomial model was developed with an area under the receiver operating characteristic curve of 0.90. CONCLUSIONS: Our data show the predictive value of BCL2, ERBB2, MYC, and TP53 in addition to the standard hormone receptors and clinicopathologic features, and they show the importance of conditional interpretation of certain molecular markers. Our multimarker predictive model performed significantly better than standard guidelines.