Correlation of Bcl-2 and p53 expression in primary breast tumors and corresponding metastatic lymph nodes

BACKGROUND: The p53 tumor suppressor gene product participated in G1 cell cycle arrest or cell death. Loss of function was associated with poor outcome in patients with breast carcinoma. bcl-2 prevented apoptosis induced by c-myc or growth factor deprivation. High bcl-2 expression in breast tumor tissue specimens appears to be associated with favorable prognostic factors. However, Bcl-2 and p53 expression in primary tumor tissue specimens versus metastatic lymph node specimens in breast carcinoma has not been studied. The current study compared Bcl-2 and p53 expression in primary breast carcinoma tissue specimens with Bcl-2 and p53 expression in axillary lymph node specimens. METHODS: Primary breast tumor and corresponding axillary metastatic lymph node tissue specimens were obtained from 60 patients with breast carcinoma. They were evaluated for the presence of Bcl-2 and p53 expression by immunohistochemistry using standard methods. RESULTS: Bcl-2 expression in primary tumor tissue specimens (53%) was correlated with Bcl-2 expression in metastatic lymph node specimens (50 %; Pearson correlation = 0.656). p53 expression in primary tumor specimens (72%) was correlated with p53 expression in metastatic lymph node specimens (60 %; Pearson correlation = 0.800). A significant inverse correlation also was found between p53 and Bcl-2 expression in primary breast tumor tissue specimens (Pearson correlation = -0.310). CONCLUSIONS: The current study suggested that Bcl-2 and p53 expression in axillary metastatic lymph node specimens is correlated with Bcl-2 and p53 expression in the primary tumor tissue specimens. The prognostic and predictive value of Bcl-2 and p53 expression in axillary lymph node metastasis in patients with breast carcinoma needs to be further evaluated in larger trials with longer follow-up.     

NH(2)-terminal truncated HER-2 protein but not full-length receptor is associated with nodal metastasis in human breast cancer.

BACKGROUND: The full-length receptor p185HER-2 undergoes a metalloprotease-dependent cleavage producing a membrane-associated fragment (p95HER-2) in cultured breast cancer cells. P95HER-2 has potentially enhanced signaling activity, but its expression and role in human breast cancer is poorly characterized. PURPOSE: The purpose of this project was to characterize the expression of p95HER-2 in primary breast cancers and nodal metastasis, and to study association with clinicopathological factors. EXPERIMENTAL DESIGN: P95HER-2 and p185HER-2 were examined in 337 primary breast tumors and 81 metastatic lymph nodes by Western blot analysis, and tested for associations with other clinicopathological factors. RESULTS: P95HER-2 was present in 20.9% of primary tumors from node-negative patients, in 29.1% from patients with one to three metastatic nodes, and in 36.7% from patients with four or more metastatic nodes (P = 0.027). Whereas p185HER-2 overexpression was unrelated to nodal disease (P = 0.63), the odds of lymph node metastasis were enhanced 2.9-fold by the presence of p95HER-2 (48.8% of node-negative versus 73.5% of node-positive patients; P = 0.03; odds ratio = 2.9). P95HER-2 was more frequent in metastatic lymph nodes than in primary tumors (45.7% versus 26.7%; P = 0.0009), whereas p185HER-2 overexpression was similar in both (22.3% versus 23.5%; P = 0.933). P95HER-2 did not significantly correlate with patient age, tumor size, stage, histotype, or hormone receptor status. CONCLUSIONS: P95HER-2 in primary tumors was related to extent of lymph node involvement and was enhanced in nodal tissue suggesting an important role as a marker or cause in breast cancer metastasis. Examination of the prognostic value of p95HER-2 in breast cancer and its coexpression with metalloprotease activity seem warranted.     

Survival of patients with metastatic breast carcinoma: importance of prognostic markers of the primary tumor

BACKGROUND: Women with metastatic breast carcinoma have a highly variable clinical course and outcome. Intrinsic genetic heterogeneity of the primary breast tumor may play a role in this variability and may explain it in part. Therefore, the authors tested the hypothesis that the characteristics of primary breast tumors are important determinants of prognosis and survival in patients with metastatic breast carcinoma. METHODS: The prognostic significance of the biology of the primary tumor for outcome in patients with metastatic breast disease was assessed in 346 patients with lymph node positive breast carcinoma who developed distant, recurrent disease. Traditional prognostic indicators (age, tumor size, number of involved lymph nodes, sites of recurrence, disease free interval [DFI], adjuvant treatments, estrogen receptor [ER] expression, progesterone receptor [PgR] expression, S-phase fraction [SPF], and DNA ploidy), together with three newer biologic markers (c-erbB-2, p53, and bcl-2) were assessed. Sites of recurrence were defined as nonvisceral (bone and locoregional lymph nodes) or visceral (lung, liver, brain, and other organs). RESULTS: The median duration of survival was 17.8 months (95% confidence interval, 15.2-21.5 months). Univariate analysis showed that age > 50 years, visceral disease, and shorter DFI were associated significantly with poor outcome (P < 0.05). In addition, the molecular phenotype of the primary breast tumor was significant, with primary tumors that showed ER negativity and PgR negativity, high SPF, aneuploidy, accumulation of p53 protein, and lower bcl-2 expression, together with c-erbB-2 overexpression, all associated with a poorer clinical outcome (P < 0.05). In a multivariate analysis, older age, visceral disease, shorter DFI, PgR negativity, high SPF, and lower bcl-2 expression were significant predictors of worse survival (P < 0.05). CONCLUSIONS: In addition to traditional risk factors, bcl-2 negativity was associated significantly with a worse clinical outcome. Biologic features of primary tumors were correlated independently with outcome after first recurrence in patients with metastatic breast carcinoma and may be used as indicators of prognosis in the metastatic setting.     

Prognostic indicators for breast cancer patients with one to three regional lymph node metastases, with special reference to alterations in expression levels of bcl-2, p53 and c-erbB-2 proteins

Patients with primary breast carcinoma with one to three axillary lymph node metastases but without distant metastases (n1-3) in Japan have been shown to have a 10-year disease-free survival rate of > 60%. It would be reasonable to divide n1-3 Japanese breast cancer patients into groups with high- or low-risk for recurrence and to consider post-operative adjuvant therapy. In the present study, we analyzed 228 consecutive Japanese patients with n1-3 breast cancer who underwent radical mastectomy and were followed up for a median time of 11.0 years. The expression of bcl-2, p53 and c-erbB-2 proteins in the primary tumors was examined immunohistochemically and their prognostic roles were also analyzed along with conventional clinicopathologic indicators. bcl-2 expression was correlated with positive estrogen receptor status and inversely correlated with p53, c-erbB-2 and histologic grade. Univariate analysis showed that bcl-2, p53 and c-erbB-2 expression were prognostic indicators of the patient's group as well as node status, histologic grade, tumor size, age at diagnosis, menopausal status and estrogen receptor status. Cox's regression analysis demonstrated that the number of nodes involved, menopausal status, p53 and bcl-2 were independent predictors for overall survival and that histologic grade and the number of nodes involved were independent predictors for disease-free survival. These results suggest that bcl-2 expression in combination with p53 and c-erbB-2 expression, the number of lymph node metastases, histologic grade and menopausal status are useful in selecting subgroups of n1-3 breast cancer patients with good or poor prognoses.      

The prognostic value of p53 and c-erbB-2 expression, proliferative activity and angiogenesis in node-negative breast carcinoma

AIMS AND BACKGROUND: p53, c-erbB-2 and Ki-67 protein expression and microvessel density (MVD) determined by CD34 antibody were evaluated by immunohistochemistry and their correlation with clinicopathological parameters including estrogen (ER) and progesterone (PR) receptor status and survival were investigated in patients with axillary lymph node-negative infiltrating ductal breast carcinoma. METHODS: The study population consisted of 47 patients with axillary lymph node-negative infiltrating ductal breast carcinoma. RESULTS: p53 and c-erbB-2 expression was detected in 36.2% and 31.9% of patients, respectively. Median Ki-67 expression was 10%. There were no statistically significant differences in the distribution of p53, Ki-67 and c-erbB-2 protein expression in relation to the age of the patients or to the size, histological grade or ER and PR status of the tumors. p53 protein expression correlated positively with c-erbB-2 and Ki-67 protein expression (P < 0.05). The mean MVD was 63.65 +/- 29.1 and it correlated positively with histological grade and Ki-67 expression (P < 0.05). Survival analysis revealed that age, tumor size, p53 and c-erbB-2 expression and PR status had no significant prognostic impact, whereas histological grade, proliferative activity and angiogenic activity were significant prognostic factors. Although ER-positive patients had a statistically significant overall survival advantage, the difference in disease-free survival was not significant. CONCLUSION: In axillary lymph node-negative breast carcinoma the histological grade and the proliferative and angiogenic activity of the tumor could be useful prognostic indicators.     

Correlation between genetic and biological aspects in primary non-metastatic breast cancers and corresponding synchronous axillary lymph node metastasis

This study investigated the changes, if any, in the level of expression of a well defined panel of cell proliferation, differentiation and apoptosis markers between the primary breast tumor and the corresponding synchronous lymph node metastasis from a population of patients with a comparable disease status, in terms of clinical features, and natural history. Ninety pure invasive ductal carcinomas with 10 or more axillary lymph nodes involved and without evidence of distant metastasis were included in this study. Primary tumor and corresponding metastatic lymph node tissue specimens were evaluated for the expression of Cyclin B1, MMP1 metalloproteinase, ICAM-1, RARβ, Ki67, ER, PgR, p53, bcl-2 and c-erbB2 by immunohistochemistry using standard methods. The bivariate Pearson correlation analysis demonstrated a close relationship between primary and matching corresponding metastatic node. A high grade of correlation has been maintained even when staining results where categorized as positive/negative according to each one marker cut-off level of staining expression. We report the most extensive immunohistochemical analysis of biological determinants in a well defined population of patients with invasive ductal carcinomas and involvement of 10 or more axillary nodes and no distant metastasis. We found a close correlation between the primary tumor and corresponding metastatic node in terms of the expression of all 10 of the markers investigated in this study. The not complete concordance observed could be explained by the gene expression modulation by extrinsic factors and by the microenvironment in which the cancer cells reside.     

Prognostic value of different factors in breast carcinoma

INTRODUCTION: The aggressive biological behavior of invasive and metastatic cancer is considered to be the most insidious and life-threatening aspect for breast cancer patients. It is mostly the result of changes in many molecular characteristics of tumor cells, including alterations in the mechanisms controlling cell growth and proliferation. AIM: The aim of this retrospective study was to identify predictors of aggressive biological behavior and metastatic potential in breast carcinoma among a number of intrinsic biomarkers of tumor cells such as steroid receptors and oncogene and tumor suppressor gene products. METHODS: Routine formalin-fixed, paraffin-embedded tumor samples were used and sections were stained immunohistochemically with the DAKO Strept ABC method to determine the expression of estrogen receptors (ER), progesterone receptors (PgR), HER-2/neu, bcl-2, Ki-67, p53 and nm23 in 192 consecutive breast carcinoma patients. The results of the quantitative immunohistochemical assays were correlated with clinical and histological data such as patient age, overall survival, tumor size, axillary lymph node status, hystological type, tumor grade, Nottingham prognostic index (NPI) and therapeutic regimens. RESULTS: Univariate analysis revealed that survival was significantly longer for patients with small tumors (P = 0.007), lower tumor grade (P = 0.021), negative axillary lymph nodes (P = 0.002), presence of nm23 protein (P = 0.002), and for patients treated with adjuvant hormonal therapy (P = 0.010). In multivariate analysis the independent factors positively affecting survival were absence of axillary lymph node metastases (P = 0.002), nm23 expression (P = 0.009) and hormonal therapy (P = 0.050). Among patients with positive axillary nodes there was a significantly higher survival rate in patients with nm23 expression compared with nm23-negative patients (P < 0.001). CONCLUSION: Identification of a subset of node-positive breast cancer patients with a more favorable prognosis according to nm23 expression might be clinically useful.     

乳腺癌合并2型糖尿病患者沉默信息调节因子1表达及其意义

 【摘要】　目的　研究沉默信息调节因子1（SIRT1）在乳腺癌合并2型糖尿病中的表达,分析其与乳腺癌合并2型糖尿病患者相关临床病理指标之间的关系。方法　应用免疫组织化学方法检测30例乳腺癌合并2型糖尿病患者、65例非糖尿病乳腺癌患者的乳腺癌组织和18例正常乳腺组织中SIRT1的表达情况。结果　SIRT1在非糖尿病、合并2型糖尿病乳腺癌组织和正常乳腺组织中的表达率分别为76.9 %（50／65）、50.0 %（15／30）、5.6 %（1／18）,乳腺癌组织均高于正常乳腺组织（χ2＝24.618,P＝0.000）,合并2型糖尿病者SIRT1的表达率低于非糖尿病患者（χ2＝6.886,P＝0.009）。合并2型糖尿病的乳腺癌患者SIRT1的表达与淋巴结转移（P＝0.011）、pTNM分期（P＝0.028）、p53蛋白的表达（P＝0.003）以及Her-2的表达（P＝0.031）均呈正相关。结论　SIRT1在乳腺癌合并2型糖尿病患者乳腺癌组织中过表达,但阳性表达率低于未合并糖尿病乳腺癌组,其可能是影响糖尿病病程进展的重要分子; SIRT1的表达与多项临床病理指标有关,可能成为判断合并2型糖尿病乳腺癌恶性程度及评估预后的生物学指标。     

Cyclooxygenase-2 expression in lymph node metastasis of cervical and vulvar cancer

Overexpression of cyclooxygenase-2 (COX-2), characterizes tumors with high potential for local invasion and lymph node involvement. We investigated the expression of COX-2 in primary tumors and metastatic regional lymph nodes (TDL) from untreated and chemotherapy treated cervical cancer, as well as vulvar cancer. Immunostaining of COX-2, expressed as values of COX-2 intensity density (COX-2 IDV) was performed on 57 metastatic TDL and 24 corresponding primary rumors from 14 cervical and 9 vulvar cancer patients admitted to the Department of Obstetrics and Gynecology, Catholic University of Rome. In 6 locally advanced cervical cancer tissue samples, from both primary tumor and TDL, were obtained after chemotherapy treatment. In untreated cervical cancer, COX-2 IDV in tumor cells from positive TDL were significantly lower (median 0.69, range 0.22-0.92) than those from primary tumors (median = 3.84, range 0.19-7.67) (p=0.011). In cervical cancer exposed to chemotherapy, COX-2 IDV in tumor cells from positive TDL were significantly lower (median = 2.06, range 1.48-6.52) than those from primary tumors (median = 6.4, range 4.5-13.7) (p=0.037). In vulvar cancer COX-2 IDV in tumor cells from positive TDL were lower (median = 0.39, range 0.02-6.09) than those from primary tumors (median = 2.49, range 0.71-8.10) (p=0.04). In conclusion, we showed that COX-2 expression is down-regulated in cervical and vulvar tumor cells invading the regional lymph nodes with respect to primary tumors, thus emphasizing the need for deeper insight into the tissue specific relation between tumor cells and node microenvironment.     

乳腺球蛋白在术前乳腺癌和腋窝淋巴结细针穿刺吸取组织中的表达及临床意义

目的 探讨乳腺球蛋白（mammaglobin,MAM）在术前乳腺癌及腋窝淋巴结细针穿刺吸取组织中的表达及临床意义.方法 对91例原发性乳腺癌行术前细针穿刺,将吸取的组织制备涂片,采用免疫组织化学方法（EnVision法）检测MAM表达,观察MAM表达与临床病理指标的关系.同时另收集15例原发性肺癌腋窝淋巴结转移患者,分析乳腺癌腋窝淋巴结转移、乳腺癌增生性淋巴结炎和肺癌腋窝淋巴结转移三者间术前腋窝淋巴结MAM表达的区别.统计分析采用χ2检验.结果 在91例原发性乳腺癌患者中MAM的阳性表达率为74.72%（68/91）.MAM的阳性表达与雌激素受体（ER）、孕激素受体（PR）、组织学分级、细胞学分级有关（P〈0.05）,与患者的年龄、肿瘤大小、淋巴结是否转移及HER-2状态无关（P〉0.05）.腋窝淋巴结观察结果显示,MAM在乳腺癌腋窝淋巴结转移患者中呈阳性表达,在乳腺癌增生性腋窝淋巴结炎和肺癌腋窝淋巴结转移患者中均为阴性表达.结论 MAM可表达于原发性和转移性乳腺癌,细针穿刺细胞学检查结合MAM的测定对乳腺癌的诊断及鉴别具有一定辅助判断价值.MAM阳性表达与ER、PR状态、细胞学分级、组织学分级有关,有利于了解肿瘤的生物学指标及判断预后.     

乳腺癌中抗癌基因p53突变及其临床预后

本研究以ｐ５３ｃＤＮＡ为探针，检测２９例散发性乳腺癌中的ｐ５３基因突变。２９例乳腺癌中有２０例乳腺癌有ｐ５３基因杂合性缺失（ＬＯＨ），缺失率为６９％。比较不同分期、肿瘤大小及ＥＲ状态的乳腺癌，ｐ５３基因缺失率无显著性差异（Ｐ＞０．０５）；而不同腋淋巴结状态的乳腺癌，ｐ５３基因缺失率有显著性差异（Ｐ＜０．０５）。上述结果表明ｐ５３基因突变是乳腺癌进程中的早期事件；ｐ５３基因的突变可能预示肿瘤具有较强的侵袭能力。     

COX-2在乳腺癌组织的表达及其与临床病理参数的相关性

目的:评价乳腺浸润性导管癌组织COX-2蛋白的表达情况及其与相关临床或病理参数间的相关性.方法:取101例资料完整的乳腺浸润性导管癌手术切除标本为研究对象,免疫组化方法检测COX-2、EGFR、cerbB-2等相关蛋白表达,采用χ2检验评估COX-2表达与不同的临床或病理参数间的关系.结果:肿瘤细胞中COX-2蛋白免疫组化阴性者15例(14.9%);阳性者86例(85.1%),COX-2高表达与乳腺癌脉管侵犯、淋巴结侵犯、分期、PR表达、cerbB-2表达及p53表达具有相关性.结论:乳腺浸润性导管癌中COX-2表达水平与肿瘤转移及分期均密切相关.     

p53 expression,growth, and spontaneous metastasis of the human GI 101 breast carcinoma in athymic nude mice

The human GI 101 breast carcinoma cell lines produces spontaneous metastasis to the lungs when xenografted subcutaneously in female athymic nude mice. To establish the time-course of tumor growth and distant metastasis to the lungs and axillary lymph nodes, 5 mm3 of tumor tissue was implanted in the subaxial region of female athymic nude mice. Micrometastases in the lung were first detected 3 weeks after tumor implantation. The incidence of lung metastasis and the number of tumor emboli were correlated with the volume of the primary tumors. Ipsilateral axillary lymph node metastasis was observed within 17 weeks, indicating that metastasis to the lymph node is a later event. Unlike pulmonary micrometastases which were in the form of clusters of four to six tumor cells, metastasis to the lymph nodes were in nodules of poorly differentiated and larger tumor cells. Immunohistochemistry evaluation of p53 oncoprotein in the primary and metastatic tumor cells showed different patterns of subcellular accumulation. Cytoplasmic staining was mainly detected in the primary and secondary tumor cells disseminated to the lungs. In contrast, nuclear staining was only detected in tumor cells infiltrated to the axillary lymph nodes. There was no gain of loss of positivity of p53 accumulation (i.e., qualitative measurements) as the tumor grew in size. The data indicate that the GI 101 tumor cells could be used as a useful model for studying the malignant progression of hormone-independent breast cancer, antimetastatic drugs, and early events in tumor metastasis.     

乳腺癌腋窝淋巴结转移血管生成的免疫组化研究

目的　研究乳腺癌腋窝淋巴结转移的血管生成情况。方法　采用内皮细胞ⅧFRAg 免疫组化染色技术,对37 例乳腺癌根治术或改良根治术切除的乳腺癌组织和121 枚腋窝转移淋巴结进行免疫组化染色。在100 倍视野下通过显微电视系统计数微血管密度( MVD) ,并用显微测量器测量转移灶的直径。结果　在121 个淋巴结中找到13 处微转移灶,其平均直径为(210 ±37) μm ,无血管生成。腋窝淋巴结转移瘤的MVD 为89-3 ±18-4 ,与乳腺癌组织MVD(93-8 ±21-8) 差异无显著性,且微血管分布不均,周围高于中央。结论　淋巴结微转移灶无血管生成,转移瘤有血管生成。为抑制微转移灶发展成转移瘤,以及抑制转移瘤的生长,抑制血管生成可能是控制淋巴结转移的有效措施。     

CCR7 and CXCR4 as novel biomarkers predicting axillary lymph node metastasis in T1 breast cancer.

PURPOSE: The chemokine receptors CCR7 and CXCR4 have been shown to play an important role in cancer metastasis. We therefore studied the differential expression of CCR7 and CXCR4, along with that of the biomarker HER2-neu, to evaluate whether these biomarkers could predict axillary lymph node metastasis in breast cancer. EXPERIMENTAL DESIGN: Biomarker expression levels were evaluated using paraffin-embedded tissue sections of lymph node-negative (n = 99) and lymph node-positive (n = 98) T1 breast cancer by immunohistochemical staining. RESULTS: Lymph node-positive tumors showed higher rates of high cytoplasmic CCR7 staining (21.5% versus 8.5%, P = 0.013) and HER2-neu overexpression (21.5% versus 9.3%, P = 0.019) than did lymph node-negative tumors. Similarly, high cytoplasmic CXCR4 expression occurred more commonly in lymph node-positive tumors (11.2% versus 5.1%, P = 0.113). In contrast, predominantly nuclear CXCR4 staining was more likely to be found in lymph node-negative tumors (54.5% versus 37.8%, P = 0.018). Furthermore, cytoplasmic CXCR4 coexpressed with HER2-neu was the only factor associated with involvement of four or more lymph nodes (16.7% versus 1.2%, P = 0.04) among lymph node-positive tumors. When all three biomarkers (CCR7, CXCR4, HER2-neu) were utilized together, 50.0% of lymph node-positive tumors highly expressed one of these biomarkers compared with 18.8% of the lymph node-negative tumors (P < 0.0001). CONCLUSIONS: Our results suggest that the chemokine receptor CCR7 is a novel biomarker that can predict lymph node metastases in breast cancer. Utilization of additional markers, such as CXCR4 and HER2-neu, further improves the prediction of the presence and extent of lymph node involvement.     

p53 protein overexpression in infiltrating ductal carcinoma of female breast and its association with lymph node metastasis

Traditionally, prognosis in carcinoma of the breast is evaluated based on size and differentiation of the tumor and status of lymph node metastasis. In addition to these established markers, in this molecular age other parameters such as overexpression of p53, c-erbB-2 and c-myc proteins are increasingly used to assess the prognosis. At present, the prognostic value of the molecular markers, at best, is controversial and conflicting. In this study, we examined 67 infiltrating ductal. carcinomas of female breast with and without lymph node metastasis for p53 protein overexpression by immunohistochemistry on formalin-fixed, paraffin-embedded tissue sections to ascertain if p53 positive tumors have greater metastatic potential than p53 negative tumors. In addition, p53 overexpression was also correlated with tumor size, grade, expression of estrogen and progesterone receptors, and age of the patient to clarify the issue of relevance of p53 overexpression in prognostication, p53 overexpression was observed in 39% of tumors and showed strong correlation only with the histological grade of the tumor. The incidence of p53 overexpression in grade 1, grade 2 and grade 3 tumors was 0%, 33% and 58% respectively. Lymph node metastasis was less frequent in tumors that overexpressed p53 protein. Twenty-seven percent of primary tumors with lymph node metastasis showed p53 protein overexpression, in contrast to 44% of tumors without metastasis. No correlation was observed between p53 overexpression and all the other parameters evaluated except progesterone receptor negative status. These results suggest that p53 overexpression is not an independent prognostic indicator and should not be used to predict lymph node metastasis or aggressive behavior of the tumor.     

Presence of breast cancer antigens in uninvolved axillary lymph nodes

Monoclonal antibodies which bind to breast cancer have been used to evaluate the detection of metastatic disease in axillary lymph nodes. Three monoclonal antibodies (H59, H71, and H72) were reacted with tissue sections of primary tumors and axillary nodes from 24 mastectomy specimens and four specimens from glandular mastectomies for benign disease. All three antibodies had been shown to react with subsets of normal and malignant breast tissue; did not bind erythroid, myeloid, or lymphoid tissue; and recognized antigens in paraffin-embedded tissue. The antibodies recognized cell surface antigens, and H59 and H72 bound to glycoproteins which are either sloughed or secreted. Primary tumors and tumors in lymph nodes from the same specimen were always bound by the same antibodies. Antibodies detected unrecognized microscopic tumor in nodes from one previously node-negative specimen and two specimens with positive nodes. This suggests that monoclonal antibodies may be useful for detecting metastatic breast cancer in nodes which by light microscopy are negative. Moderate binding of H59 and H72 antibodies to sinus histiocytes and perivascular cells was observed in all uninvolved nodes with sinus hyperplasia obtained from benign and malignant specimens. Thus, breast antigens can be identified in hyperplastic nodes in patients with no evidence of breast cancer. The antigens are detected predominately in the lymphoid sinuses and are bound to nonneoplastic cells. Therefore, breast antigens are regularly being processed and presented by normal lymphoid cells within the sinus. The binding of these monoclonal antibodies to axillary lymph nodes does not necessarily indicate the presence of metastatic disease. Dense binding to paracortical single cells was observed in tumor-containing lymph nodes and in uninvolved nodes obtained from mastectomy specimens with breast cancer. These cells are infrequent, and their number in an uninvolved node correlates with the pathological stage. They represent either binding to isolated lymphoid cells or metastatic tumor. Studies are under way to determine the origin of these cells.     

p53 、bcl-2 和CD44v6 蛋白表达与乳腺癌转移的相关性研究

 目的 探讨乳腺癌及癌旁正常乳腺组织中p53、bcl—2和CD44v6蛋白的表达及意义。方法 采用免疫组化法检测96例乳腺癌及其癌旁正常乳腺组织中p53、bcl—2和CD44v6蛋白的表达，并分析其与淋巴结转移和c-erbB-2表达状态的相关性，从而评价这些指标在预测乳腺癌转移方面的价值。结果 正常乳腺组织中p53蛋白为阴性，在乳腺癌中阳性表达率为65．63％；随着组织学分级的增高，阳性率逐渐增高；淋巴结转移组阳性表达率明显高于无淋巴结转移组，并与c-erbB-2表达状态呈正相关。乳腺癌组织中bcl-2阳性表达率明显低于周围正常乳腺组织，随着组织学分级的增高，阳性率逐渐降低，淋巴结转移组中的表达率明显低于淋巴结非转移组，与c-erbB-2的表达呈负相关。CD44v6在乳腺癌组织中的阳性表达率明显高于正常乳腺组织，随着组织学分期的增加，CD44v6的阳性表达率亦增高，但差异无显著性，淋巴结转移组的阳性率略高于无淋巴结转移组，差异也无显著性，与c-erbB-2表达无相关性。结论 p53和bcl-2蛋白可作为预测乳腺癌转移的指标，CD44v6的阳性表达可能与乳腺癌的发生、进展有一定关系，但尚不能把它作为预测乳腺癌转移的稳定的生物学指标。     

COX-2与突变型p53蛋白在乳腺癌组织中的表达及临床意义

目的研究COX-2蛋白和突变型p53蛋白在乳腺癌组织中的表达情况,探讨两者在乳腺癌发生、发展中的作用、相互关系及与临床病理学特征之间的关系。方法运用链霉菌抗生物素蛋白-过氧化物酶免疫组织化学方法（S-P）对99例乳腺癌组织中COX-2蛋白和突变型p53蛋白的表达进行检测。结果99例乳腺癌中COX-2蛋白表达阳性率为69.7%（69/99）,COX-2蛋白表达与患者年龄、原发肿瘤大小、腋淋巴结转移状况、TNM临床分期、激素受体状况均无显著相关（P〉0.05）,而与C-erbB-2蛋白表达呈显著相关（P〈0.05）。99例乳腺癌中突变型p53蛋白表达阳性率为48.5%（48/99）,突变型p53蛋白表达与患者年龄、TNM临床分期、激素受体状况无显著相关（P〉0.05）,而与原发肿瘤大小、腋淋巴结转移状况、C-erbB-2蛋白表达呈显著相关（P〈0.05）。COX-2蛋白表达与突变型p53蛋白在乳腺癌组织中的表达呈正相关（r=0.288,P〈0.05）,两者共表达与肿瘤大小、腋淋巴结转移状况呈显著相关（P〈0.05）。结论COX-2蛋白和突变型p53蛋白在乳腺癌组织中高表达,COX-2蛋白与突变型p53蛋白在乳腺癌组织中的表达呈正相关,两者在乳腺癌的发生、发展中可能起协同作用,是反映乳腺癌生物学行为的重要指标。