Mutual predictive value of c-erbB-2 overexpression and various prognostic factors in ductal invasive breast carcinoma

AIMS AND BACKGROUND: Breast carcinoma is a heterogeneous disease, the prognosis of which correlates with various prognostic factors. The aim of this study was to assess the prognostic significance of c-erbB-2 overexpression in breast carcinoma patients in association with other known prognostic factors. METHODS & STUDY DESIGN: The relationship between immunohistochemical expression of the c-erbB-2 oncoprotein and various established prognostic factors such as tumor size, axillary node status, estrogen and progesterone receptor status, DNA ploidy, proliferation index, cathepsin D expression and histological grade in invasive ductal breast carcinoma is presented in this study. RESULTS: Of the 93 ductal invasive carcinomas 22 (23.7%) were grade I, 51 (54.8%) grade II, and 20 (21.5%) grade III, and the majority (78: 83.9%) were 2-5 cm in diameter. Tumor metastases were identified in one or more lymph nodes in 55 (59.1%) patients, the remaining 38 (40.9%) patients being lymph node negative. According to the DNA histograms 40 (43.0%) tumors were aneuploid and 53 (57.0%) were diploid, and the majority of tumors had more than 4% of cells in the S phase of the cell cycle (83.9%). Expression of c-erbB-2 as shown by immunohistochemical intense membrane staining was present in 49 (52.7%) tumors. Cathepsin D-positive cytoplasmic granular staining and cathepsin D-positive stromal macrophages were found in 60 (64.5%) and 72 (77.4%) tumors, respectively. Univariate analysis showed that overall survival correlated significantly with axillary lymph node involvement and with estrogen and progesterone receptor status for each of the receptors separately and for their coexpression, and only marginally with c-erbB-2 overexpression. In mulitivariate analysis only axillary lymph node metastases and coexpression of estrogen and progesterone receptors were found to be independent and significant prognostic factors. CONCLUSIONS: When patients were stratified according to c-erbB-2 expression it was shown that those with c-erbB-2 overexpression and grade II tumors, tumor size greater than 2 cm, high content of aneuploid cells and cathepsin D-positive stromal macrophages had a shorter long-term survival than c-erbB-2 negative patients.     

C-erbB-2 overexpression in primary breast cancer: independent prognostic factor in patients at high risk

Summary The prognostic value of c-erbB-2 protein overexpression has been evaluated in 463 patients with operable breast cancer after a median follow-up of 66 months. Overexpression was observed in 99/463 (21%) of the breast tumors. It showed significant positive correlation to histological grade (p < 0.0001) and tumor size (p < 0.02). A relationship of borderline significance was observed between c-erbB-2 protein overexpression and negative or low estrogen receptor (ER) content. No significant correlation was found to lymph node involvement or proliferating tumor cell fraction as determined by the proliferating cell nuclear antigen (PCNA). After a median follow-up of 66 months (range 6 to 109 months), the overall survival of all patients amounted to 63%. Multivariate analysis revealed lymph node involvement, tumor size, histological grade, histological type, c-erbB-2 protein overexpression, progesterone receptor (PR) content, and oral contraceptive use as independent prognostic factors. In an univariate analysis, the overall survival amounted to 72% and 38% of tumor patients with negative and positive c-erbB-2 protein overexpression, respectively. The most significant finding is that c-erbB-2 overexpression has been recognized as an independent predictive factor in subsets of tumor patients who would be expected to have a generally poor prognosis, such as those indicating axillary lymph node involvement, large tumor size (> 2 cm), and PR negativity.     

Risk factors of metastasis in oral squamous cell carcinomas

Lymph node and distant metastasis were comparatively studied in 225 oral carcinomas, and factors predisposing toward metastasis were investigated using clinical and immunohistopathological approaches. Neither the sites of tumors nor T-stage was correlated with either type of metastasis. Tumor cell differentiation was weakly correlated with lymph node metastasis, and stromal reaction (the degree of cell infiltration) did not differ greatly between metastasis-positive and negative tumors, although natural killer (NK) activities were correlated with lymph node metastasis. However, the mode of tumor cell invasion was closely associated with both lymph node and distant metastases. In grade 4C and 4D tumors, distant and lymph node metastases were observed in 8 (16%) and 31 (62%) cases, respectively, while of 68 grade 1 and 2 tumors, distant metastasis was not observed in any, and lymph node metastasis occurred in only 15 (22. 1%). In addition, the expression of p53 protein was correlated with lymph node metastasis; of 70 tumors without p53 protein expression, 23 (32.9%) revealed lymph node metastasis, while it occurred in 54 out of 96 tumors positive for p53 protein. However, p53 protein expression was not associated with distant metastasis, and p24 protein, a cyclin-dependent kinase inhibitor, did not show any relationship with either type of metastasis. These results indicate that lymph node metastasis is correlated with multiple factors in the host and tumor cells, but distant metastasis is only correlated with the mode of tumor cell invasion, suggesting that the former can be highly accurately predicted by invasion mode, p53 protein expression and NK activity.     

Biologic behavior of and p53 overexpression in multifocal renal cell carcinoma of clear cell type: an immunohistochemical study correlating grading, staging, and proliferation markers

BACKGROUND: In the treatment of small renal cell carcinoma (RCC), there is controversy between radical and nephron-sparing surgical treatment because of the risk of tumor multifocality. The biologic behavior of multifocal RCC compared with that of unifocal RCC is not well investigated, and the relevance of p53 and the proliferation markers MIB-1 and proliferating cell nuclear antigen (PCNA) to multifocal RCC is not yet established. METHODS: In this study, p53 protein overexpression was investigated immunohistochemically in 27 multifocal and 65 unifocal clear cell RCCs using a monoclonal antibody (DO-1). The nuclear expression of p53 was compared with the expression of PCNA and MIB-1 (Ki-67 antigen) and other prognostic factors, including grade and stage. RESULTS: Thirty-three RCCs (35.9%) had p53 positive nuclear staining. MIB-1 positivity was significantly higher in p53 positive tumors than in p53 negative tumors. PCNA positivity was not different in p53 positive tumors compared with p53 negative tumors. Proliferation marker expression was not associated with tumor focality. p53 overexpression was more often found in unifocal tumors than in multifocal tumors. Intracellular accumulation of the p53 protein was related to tumor grade but not to the T classification of tumor stage. In addition, lymph node involvement was significantly associated with p53 overexpression in tumors of the kidney. Focality did not influence progression free survival. CONCLUSIONS: This study demonstrated that there is no difference in the proliferative activity or biologic behavior of multifocal and unifocal tumors.     

Correlations between HER2 Expression and Other Prognostic Factors in Breast Cancer: Inverse Relations with the Ki-67 Index and P53 Status

Background: Overexpression or amplification of human epidermal growth factor receptor-2 (HER2) is associated with grade of malignancy and a poor prognosis in breast cancer (BC). The aim of this study was to evaluate of value of HER2 as a prognostic marker, and to analyze associations with common histopathological parameters in BC cases. Materials and Methods: Between of 2007 to 2014, 260 patients with BC referred to Oncology Clinic provided cancer tissue samples which underwent immunohistochemistry (IHC) for markers. ER and PR positivity was defined as 10% positive tumor cells with nuclear staining. HER2-positive was defined as either HER2 gene amplification by fluorescent in situ hybridization (FISH) or scored as 3 by IHC. For HER2 (2), FISH was performed to determine HER2 positivity. Results: The mean age at diagnosis for the patients with HER2-negative was significantly higher than in HER2-positive cases. Also, there were significant correlations between histological grade, nuclear grade, lymph node metastasis, tumor size, ER status, PR status, p53 overexpression and Ki-67 index with HER2 expression. HER2-negative lesions were of higher grade and more likely to be ER-negative, PR-negative, p53-positive, lymph node metastasis, with a tumor sizealso Ki-6720% as compared to the HER2-positive group. Conclusions: Contrary to the results of other studies, HER2-positive tumors in our study had a lower Ki-67 index and were p53-positive. Also, Ki-67 proliferation index 20% in more studies was associated with p53-positive.Therefore, tumors which are HER2-positive and have a Ki-6720% had a more aggressive behavior compared to HER2-positive and Ki-67<20% lesions.     

nm23 and p53 expression

Breast cancer is a common malignancy and the modalities and the aggressiveness of treatment strategies are variable and depend on information regarding the biological characteristics and behavior of an individual tumor. Therefore, to improve overall survival it is important to identify and select lymph node negative patients at high risk who would benefit from adjuvant therapy. Besides prognostic factors such as lymph node status, hormone receptor status and histopathologic parameters, nm23 antimetastatic gene and the p53 protein were studied in 32 breast cancer patients. Positive staining for nm23 was inversely associated with lymph node involvement in 82.4% of the cases. Most of the non-diploid lesions (70.8%) showed a high protein expression. Positive immunostaining for p53 was present in 28.1% of the cases and was strongly correlated with prognostic indicators such as necrosis and histologic grading. Tumor grade, DNA ploidy and lymph node metastasis were not significantly correlated with p53 protein expression. In this study, all the prognostic indicators studied, satisfactorily explain the important characteristics of the biologic behaviour of breast cancer, but the detection of lymph node metastasis is still the most accurate prognostic factor utilized for a predictive role in disease recurrence.     

Decreased immunoreactivity for p27 protein in patients with early-stage breast carcinoma is correlated with HER-2/neu overexpression and with benefit from one course of perioperative chemotherapy in patients with negative lymph node status: results from International Breast Cancer Study Group Trial V

BACKGROUND: The objective of this study was to clarify the prognostic and predictive value of immunoreactivity for the cyclin-dependent kinase inhibitor p27(Kip1) in patients with early-stage breast carcinoma and to investigate its relation with clinicopathologic features and other markers. METHODS: Immunoreactivity for p27 protein was analyzed on tumor slides from 461 patients who were enrolled in the International Breast Cancer Study Group (IBCSG) Trial V (median follow-up, 13 years), including 198 patients with lymph node negative disease and 263 patients with lymph node positive disease. Tumors with < 50% immunoreactive neoplastic cells were considered low expressors. Immunoreactivity for p27 was correlated with several clinicopathologic characteristics. Disease free survival (DFS) and overall survival were analyzed according to p27 immunoreactivity and treatment group. RESULTS: In the lymph node negative population, decreased p27 immunoreactivity was associated with higher tumor grade (P = 0.001) and HER-2/neu overexpression (P = 0.04). In the lymph node positive population, low p27 expression was associated with higher tumor grade (P = 0.01), low expression of thymidylate synthase (P = 0.001), and higher Ki-67 expression (P = 0.007). DFS was not significantly different according to p27 status in either lymph node negative patients (10-year DFS: low p27 expression, 53% +/- 5%; high p27 expression, 55% +/- 5%) or in lymph node positive patients (10 year DFS: low p27 expression, 33% +/- 4%; high p27 expression, 32% +/- 4%). However, in the lymph node negative population, the benefit of one course of perioperative chemotherapy with cyclophosphamide, methotrexate, and 5-fluorouracil was confined exclusively to patients with tumors that showed reduced p27 immunoreactivity (P = 0.03; test for interaction). CONCLUSIONS: This analysis indicates that p27 immunoreactivity has little if any prognostic value in patients with early-stage breast carcinoma. However, these findings suggest that, in patients with breast carcinoma who have negative lymph node status, reduced p27 immunoreactivity is associated with HER-2/neu overexpression and may be predictive of a benefit from the early administration of adjuvant chemotherapy.     

MYC overexpression and poor prognosis in sporadic breast cancer with BRCA1 deficiency

Breast cancer is a complex disease; the molecular mechanisms involved in sporadic breast carcinogenesis remain to be elucidated. The present study aimed to explore the deficiency of breast cancer susceptibility gene 1 (BRCA1), including protein loss expression, promoter hypermethylation and gene copy deletion, its correlationship with other tumor markers expression (TP53, MYC, etc.), and clinical significance in sporadic breast cancer. BRCA1 protein expression was negative in 226 of 374 (60.4 %) cases of this study. Cases negative for BRCA1 protein were more often with pathological tumor–node–metastasis stage III, positive for lymph node metastasis and MYC overexpression than BRCA1-positive tumors. BRCA1 hypermethylation was detected in 16.4 % (31 of 189) breast cancers, which correlated with BRCA1 negative, ER negative, MYC overexpression, and triple-negative phenotype. In addition, the percentage of cells with BRCA1 gene copy deletion was significantly increased in BRCA1-methylated tumors. Kaplan–Meier survival analysis showed that patients with BRCA1-negative expression showed a worse overall survival (OS) than those with BRCA1-positive expression, and patients with BRCA1-methylated tumors had a significantly worse disease-free survival than did patients with unmethylated tumors. Furthermore, BRCA1 hypermethylation showed an inverse association with OS in LN-positive or p53-negative subgroup patients. Importantly, uni- and multivariate Cox regression analyses revealed that BRCA1 was an independent prognostic indicator of OS in sporadic breast cancer. Thus, we found MYC overexpression and poor prognosis in sporadic breast cancer with BRCA1 deficiency. The targeting of BRCA1 deficiency in combination with MYC–pathways inhibitors may provide a promising strategy for sporadic breast cancer care, the triple-negative subtype in particular.     

178例三阴性乳腺癌的临床病理特征及生存分析

 目的
探讨三阴性乳腺癌(TNBC)患者的临床病理特点、生存情况和预后影响因素。方法收集雌激素受体(ER)、孕激素受体
(PR)和人表皮生长因子受体2(HER2)均阴性的178例乳腺癌患者的临床病理资料,观察其长期生存状况。分析其临床
特点及影响预后的因素。结果有乳腺癌家族史的患者4例。主要病理类型为浸润性导管癌(155/178,87.1%）。组织
学分级多为Ⅲ级(53.1%）。中位肿瘤最大径2.8 cm(0.2～12 cm）,T1、T2期患者160例占89.9%。108例(61.7%）
患者无淋巴结转移。分期为Ⅰ、Ⅱ、Ⅲ期的患者分别有60例(33.7％)、81例(45.5％)、31例(17.4％)。58例(48.3
％)患者p53阳性。中位随访时间74月(10～156月）,5年
无病生存(DFS)和总生存(OS)率分别是76.9%和86.1%。单因素分析显示T分期、临床分期及淋巴结转移对DFS和OS
均有显著影响。多因素分析显示,淋巴结转移是DFS及OS的独立影响因素。而术后分期是OS的影响因素。共有41例
患者出现复发转移及第二原发肿瘤,常见转移部位依次为骨转移、局部复发或同侧锁骨上淋巴结转移、肺或胸膜转
移、肝转移及脑转移。结论 本组TNBC肿瘤直径较小,组织学分级低分化比例较高(53.1%）。复发转移以骨转移、
局部复发及肺转移为主。淋巴结转移及术后分期是总生存的独立危险因素。     

Tissue microarray analysis of connexin expression and its prognostic significance in human breast cancer

Breast cancer accounts for approximately 15% of all cancer deaths. Currently, axillary nodal status is the most reliable prognostic indicator for breast cancer. Tumor size and histological grade are used to stage breast cancer. Estrogen receptor/progesterone receptor (ER/PR) and HER-2/neu status are useful in predicting patient survival and relapse. Ki67, an indicator of proliferative activity, also correlates well with prognosis. Connexin proteins form gap junction channels, permitting intercellular exchange of ions and small molecules. Reduced connexin protein levels and impaired gap junctional intercellular communication are associated with tumor phenotypes. This study investigated the prognostic value of connexin proteins as breast cancer markers. Tissue microarrays, containing 438 cases of invasive breast carcinoma, were stained with Cx26, Cx32, and Cx43 antibodies. The degree of connexin immunoreactivity was determined and then correlated with patient outcome, tumor grade, tumor size, lymph node status, and immunohistochemical markers, such as p53, ER/PR status, Ki67 and c-erbB-2 expression. Cx26, Cx32, or Cx43 did not correlate well with tumor grade, tumor size, p53 or c-erbB-2 status. There was an inverse correlation between Cx32 and lymph node status (P <0.05) and a positive correlation between Cx43 and PR status (P <0.01). Cx32 and Cx43 correlated positively with ER status (P <0.01). Cx43 correlated negatively with Ki67 expression (P <0.01). Cx26, Cx32, and Cx43 did not correlate with patient outcome. Based on our observations in this study, connexin proteins do not appear to be reliable indicators of breast cancer prognosis.     

Prognostic markers in triple-negative breast cancer

BACKGROUND: Triple-negative breast cancer (estrogen receptor-negative, progesterone receptor-negative, and HER2-negative) is a high risk breast cancer that lacks the benefit of specific therapy that targets these proteins. METHODS: In this study, the authors examined a large and well characterized series of invasive breast carcinoma (n = 1944) with a long-term clinical follow-up (median, 56 months) by using tissue microarray. The series were also stained with concurrent immunohistochemical prognostic panels (estrogen receptor, progesterone receptor, HER-2, androgen receptor, epidermal growth factor receptor (EGFR), P-cadherin, E-cadherin, and basal (CK5/6, CK14), and p53), to characterize this specific subgroup of breast cancer and to identify prognostic markers that can identify tumors with more aggressive behavior. RESULTS: Of informative cases, 16.3% were of the triple-negative phenotype. The majority of these tumors were grade 3, ductal/no-specific-type carcinomas. There were positive associations with larger size, pushing margins, poorer Nottingham Prognostic Index, development of recurrence and distant metastasis, and poorer outcome. In addition, associations were found with loss of expression of androgen receptor and E-cadherin, and positive expression of basal cytokeratins (basal phenotype), P-cadherin, p53, and EGFR. In all tumors, tumor size, lymph node stage, and androgen receptor were the most useful prognostic markers. In the lymph node-positive subgroup, both size and androgen receptor retained their prognostic significance. However, in the lymph node-negative tumors, basal phenotype was the sole prognostic marker identified in this subgroup. Other parameters including age, histological grade, tumor size, vascular invasion or other biomarkers included in the current study were not significant. CONCLUSIONS: The authors concluded that assessment of androgen receptor and basal phenotype, in addition to the established pathologic variables, mainly lymph node status and tumor size, can be used to select high-risk and low-risk patients at the time of primary surgery and can provide valuable information on treatment options in these triple-negative tumors.     

乳腺浸润性导管癌^（18）F-FDG摄取的影响因素分析

目的：探讨肿瘤大小、病理分级、有无淋巴结转移及病理分子标志物雌激素受体（ER）、孕激素受体（PR）、表皮生长因子受体（C-erbB-2）、p53抑癌基因（p53）及增殖细胞核抗原Ki67（Ki67）对乳腺浸润性导管癌18F-FDG摄取的影响。方法：37例病理证实乳腺浸润性导管癌术前18F-FDG PET/CT SUVmax与术后病理免疫组化结果进行综合分析,采用Mann-Whitney U检验进行统计学分析。结果：病灶直径≥2.5cm、肿瘤高分化（III级）、淋巴结转移组平均SUVmax分别高于〈2.5cm、低分化（I-II级）及淋巴结未转移有统计学意义（P〈0.05）。ER（﹣）组18F-FDG摄取程度高于ER（﹢）组（P〈0.05）,Ki67（﹢）组18F-FDG摄取程度高于Ki67（﹣）组,差异均有统计学意义（P〈0.05）。而PR、C-erbB-2及p53对18F-FDG摄取影响不明显。结论：乳腺浸润性导管癌病灶大小、病理分级、有无淋巴结转移、ER、Ki67的表达影响18F-FDG摄取,18F-FDG PET/CT鉴别诊断及初步分期时应引起重视。     

乳腺浸润性导管癌18F-FDG摄取的影响因素分析

目的:探讨肿瘤大小、病理分级、有无淋巴结转移及病理分子标志物雌激素受体(ER)、孕激素受体(PR)、表皮生长因子受体(C-erbB-2)、p53抑癌基因(p53)及增殖细胞核抗原Ki67(Ki67)对乳腺浸润性导管癌18F-FDG摄取的影响。方法:37例病理证实乳腺浸润性导管癌术前18F-FDG PET/CT SUVmax与术后病理免疫组化结果进行综合分析,采用Mann-Whitney U检验进行统计学分析。结果:病灶直径≥2.5cm、肿瘤高分化(III级)、淋巴结转移组平均SUVmax分别高于<2.5cm、低分化(I-II级)及淋巴结未转移有统计学意义(P<0.05)。ER(﹣)组18F-FDG摄取程度高于ER(﹢)组(P<0.05),Ki67(﹢)组18F-FDG摄取程度高于Ki67(﹣)组,差异均有统计学意义(P<0.05)。而PR、C-erbB-2及p53对18F-FDG摄取影响不明显。结论:乳腺浸润性导管癌病灶大小、病理分级、有无淋巴结转移、ER、Ki67的表达影响18F-FDG摄取,18F-FDG PET/CT鉴别诊断及初步分期时应引起重视。     

血管内皮生长因子和抑癌基因p53在胃癌中的表达及其临床意义

目的 :研究血管内皮生长因子 (vascularendothelialgrowthfactor,VEGF)和抑癌基因p53表达的的相关性 ,与胃癌临床病理学指标的关系及其联合表达对胃癌患者预后的影响。方法 :应用免疫组化法同时检测 1 0 8例胃癌组织VEGF和P53蛋白表达水平。结果 :本组病例VEGF蛋白表达阳性率为 53 .7% ,P53蛋白表达阳性率为 57.4 % ,且两者呈正相关 (P <0 .0 1 )。VEGF蛋白表达水平与浆膜浸润、淋巴结转移和TNM分期有关 (P <0 .0 1 )。P53蛋白表达水平与患者年龄、肿瘤部位、脉管侵犯、浆膜浸润、淋巴结转移和TNM分期有关 (P <0 .0 5)。并且两者的表达和胃癌患者的预后呈负相关 (P <0 .0 1 )。结论 :VEGF和P53蛋白的表达呈正相关和胃癌的生物学特性有关 ,可作为估计胃癌预后的重要因素     

Prognostic variables in patients who have undergone radical cystectomy for transitional cell carcinoma of the bladder

OBJECTIVE: To evaluate whether several clinicopathological factors could be used as prognostic predictors in patients who have undergone radical cystectomy for transitional cell carcinoma (TCC) of the bladder. METHODS: Between January 1985 and June 2000, 154 patients underwent radical cystectomy and pelvic lymphadenectomy for TCC of the bladder at a single institution. Their clinicopathological findings were analyzed based on the criteria of the Japanese Urological Association. RESULTS: Histopathological examination revealed that the tumor grade was 1 or 2 in 22 patients and 3 in 132 patients; the pathological stage was pT1 or less in 30 patients, pT2 in 51 patients, pT3 in 53 patients and pT4 in 20 patients. Vascular involvement and lymph node metastasis were found in 85 and 33 patients, respectively. The cause-specific 5-year survival rate was 64.2% for all patients, 74.4% for patients with grade 1 or 2 tumors, 62.9% for those with grade 3 tumors; 90.9% for those with stage pT1 or less, 77.9% for those with stage pT2, 45.0% for those with stage pT3 and 29.2% for those with stage pT4 (p < 0.001); 83.2% for patients without vascular involvement and 42.0% for those with vascular invasion (p < 0.001); and 76.5% for patients without lymph node metastasis and 22.7% for those with lymph node metastasis (p < 0.001). Multivariate analysis revealed a strong independent correlation of the pathological stage and lymph node metastasis with poor prognosis and, furthermore, the incidence of lymph node metastasis was significantly related to the increase in pathological stage. CONCLUSIONS: In this series, the pathological stage, lymph node metastasis and vascular involvement, but not tumor grade, were significantly useful prognostic factors in patients who have undergone radical cystectomy for TCC and among them only pathological stage and lymph node metastasis could be used as independent predictors for poor prognosis.     

Hormone receptor loss in endometrial carcinoma curettage predicts lymph node metastasis and poor outcome in prospective multicentre trial

BackgroundPreoperative histologic examination of tumour tissue is essential when deciding if endometrial cancer surgery should include lymph node sampling. We wanted to investigate if biomarkers could improve prediction of lymph node metastasis and outcome.Patients and methodsCurettage specimens from 832 endometrial carcinoma patients prospectively recruited from 10 centres in the MoMaTEC trial (Molecular Markers in Treatment of Endometrial Cancer) were investigated for hormone receptor and p53 status.ResultsEighteen per cent of tumours were double negative for oestrogen- and progesterone receptors (ER/PR loss), 24% overexpressed p53. Pathologic expression of all markers correlated with nodal metastases, high FIGO (Federation International of Gynecology and Obstetrics) stage, non-endometrioid histology, high grade and poor prognosis (all P < 0.001). ER/PR loss independently predicted lymph node metastasis (odds ratios (OR) 2.0, 95% confidence interval (CI) 1.1–3.7) adjusted for preoperative curettage histology and predicted poor disease-specific survival adjusted for age, FIGO stage, histologic type, grade and myometrial infiltration (hazard ratio (HR) 2.3, 95% CI 1.4–3.9). For lymph node negative endometrioid tumours, ER/PR loss influenced survival independent of grade.ConclusionDouble negative hormone receptor status in endometrial cancer curettage independently predicts lymph node metastasis and poor prognosis in a prospective multicentre setting. Implementing hormone receptor status to improve risk-stratification for selecting patients unlikely to benefit from lymphadenectomy seems justified.     

ER,EGFR,p53在乳腺癌组织中的比较研究

采用免疫组化染色技术,检测７５例原发乳腺癌组织中雌激素受体（ＥＲ）,表皮生长因子受体（ＥＧＦＲ）及ｐ５３的表达。结果表明：ＥＲ、ＥＧＦＲ、ｐ５３的阳性表达率分别为４９．３％、４１．３％和３７．３％。ＥＲ、ＥＧＦＲ的表达与腋淋巴结转移、临床分期有明显相关性（Ｐ＜０．０５）;与年龄及肿瘤大小无明显相关性（Ｐ＞０．０５）。ＥＧＦＲ与ＥＲ有负相关性（Ｐ＜０．０５）。在有４个以上腋淋巴结转移的２１例病例中,ＥＧＦＲ阳性者１４例,占６６．７％。２０例临床Ⅲ期的病例,ＥＧＦＲ阳性者１５例,占７５．０％。ｐ５３的表达与腋淋巴结转移、临床分期、年龄及肿瘤大小均无明显相关性（Ｐ＞０．０５）;与ＥＲ呈负相关性（Ｐ＜０．０５）;与ＥＧＦＲ呈正相关性（Ｐ＜０．０５）。研究认为ＥＧＦＲ蛋白表达阳性的乳腺癌病人预后不良,ｐ５３蛋白表达阳性与乳腺癌病人的预后无明显相关性。     

Histopathologic findings predicting lymph node metastasis and prognosis of patients with superficial esophageal carcinoma: analysis of 240 surgically resected tumors

BACKGROUND: If it were possible to elucidate the histopathologic findings predicting lymph node metastasis and prognosis in superficial squamous cell carcinoma of the esophagus (SSCCE), they could be used as markers to identify patients who do not require additional surgical resection after endoscopic mucosal resection (EMR). METHODS: Two hundred forty surgically resected SSCCEs were examined histopathologically. Histopathologic factors including vertical tumor invasion depth in the submucosal layer (VTIDsm), degree of nuclear atypia (low, one point; high, two points), growth pattern (expansive, one point; infiltrative, two points), and histologic grade (calculated by adding the latter two scores to obtain Grade 1, two points; Grade 2, three points; and Grade 3, four points) were evaluated to investigate the associations among these factors, lymph node metastasis, and prognosis. RESULTS: No lymph node metastasis was found in 54 patients with carcinoma limited to the lamina propria. Their 5-year survival rate was 100%. Multivariate analysis of 186 carcinomas invading beyond the lamina propria showed that lymphatic permeation correlated with lymph node metastasis (P<0.0001) and the presence of lymph node metastasis and a high histologic grade were independent factors indicating a poor prognosis (P = 0.0061 and 0.023, respectively). In 53 patients whose tumors had invaded the lamina muscularis or slightly invaded the submucosa (VTIDsm <500 microm), no lymph node metastasis was found in the lymphatic permeation negative and blood vessel permeation negative patients with VTIDsm values <200 microm and histologic Grades 1 or 2. CONCLUSIONS: Lymphatic permeation is a good predictor of lymph node metastasis in patients with SSCCE. Lymph node metastasis and the histologic grade are independent prognostic factors. Vessel permeation, VTIDsm, and histologic grade were found to be important factors for identifying patients who did not require additional surgical treatment after EMR.     

Expression of p53 Breast Cancer in Kurdish Women in the West of Iran: a Reverse Correlation with Lymph Node Metastasis

Background: In breast cancer (BC), it has been suggested that nuclear overexpression of p53 protein might be an indicator of poor prognosis. The aim of the current study was to evaluate the expression of p53 BC in Kurdish women from the West of Iran and its correlation with other clinicopathology figures. Materials and Methods: In the present retrospective study, 231 patients were investigated for estrogen receptor (ER) and progesterone receptor (PR) positivity, defined as 10% positive tumor cells with nuclear staining. A binary logistic regression model was selected using Akaike Information Criteria (AIC) in stepwise selection for determination of important factors. Results: ER, PR, the human epidermal growth factor receptor 2 (HER2) and p53 were positive in 58.4%, 55.4%, 59.7% and 45% of cases, respectively. Ki67 index was divided into two groups: 54.5% had Ki67<20% and 45.5% had Ki67 20%. Of 214 patients, 137(64%) had lymph node metastasis and of 186 patients, 122(65.6%) had vascular invasion. Binary logistic regression analysis showed that there was inverse significant correlation between lymph node metastasis (P=0.008, OR 0.120 and 95%CI 0.025-0.574), ER status (P=0.006, OR 0.080, 95%CI 0.014-0.477) and a direct correlation between HER2 (P=005, OR 3.047, 95%CI 1.407-6.599) with the expression of p53. Conclusions: As in a number of studies, expression of p53 had a inverse correlation with lymph node metastasis and ER status and also a direct correlation with HER2 status. Also, p53-positivity is more likely in triple negative BC compared to other subtypes.     

Impact of Triple Negative Phenotype on Prognosis and Early Onset of Breast Cancer in Iranian Females

Background: Breast cancer in Iranian women occurs about a decade earlier than in Western countries. Thisstudy sought to evaluate the impact of triple negative phenotype on early onset of ductal cell breast cancer and itsprognosis in Iranian females. Methods: Estrogen and progesterone receptors, Her-2 overexpression and nuclearaccumulation of P53 were assessed in sixty surgically resected formalin-fixed paraffin embedded breast invasiveductal carcinomas. They were divided into triple negative and non triple negative phenotypes and impact of thephenotypes were evaluated on prognostic factors of all patients and based on menopausal status. Results: Theresult showed that the mean age of patients with triple negative breast tumors, especially in postmenopausalgroup, was significantly lower than with non triple negative phenotypes. Although the latter was significantlyassociated with higher histological grade, it also showed a significant correlation with smaller size of tumor anda lower rate of axillary lymph node metastasis in young patients. Conclusion: The higher rate of breast cancerwith triple negative phenotype in Iranian females is a feasible reason for the reported lower mean age of breastcancers. In premenopausal patients, triple negative phenotype reveals a positive impact on prognostic factors,but it is associated with a poorer prognosis in postmenopausal patients. Hence, a distinct ethnic profile of triplenegative phenotype in Iranian females is suggested.