Lack of c-erbB-2 oncoprotein expression in male breast carcinoma.

A series of 21 male breast carcinomas were immunostained using NCL-CB11, an antibody directed against the internal domain of the c-erbB-2 transmembrane oncoprotein. In contrast to female breast cancer, where up to 35% of cases show positivity, all of these cases were negative. This suggests that no prognostic information regarding patient survival can be made in these patients and that male breast carcinomas may be under different growth control mechanisms from female breast carcinomas.     

Prognostic value of c-erbB-2 expression in uterine cervical carcinoma.

AIMS: To study the pattern of expression and prognostic importance of c-erbB-2 protein in cervical carcinoma. METHODS: Sixty two cases of stage IB/IIA cervical carcinoma, representing the three main tumour types, were investigated immunohistochemically for the presence of c-erbB-2 protein expression, using a monoclonal antibody (CB11) to its internal domain. Follow up of at least five years' duration was available in all cases. RESULTS: Definite membrane staining was seen in 38.7% of cases. There was a strong correlation with poor survival (p less than 0.0001) particularly. For those with adenocarcinomas, this was the case when nodal metastases were present. In contrast, for squamous carcinomas and adenosquamous carcinomas, the association with a poor prognosis was most apparent in those patients without lymph node metastases. CONCLUSIONS: These findings raise the possibility that immunostaining for c-erbB-2 protein could be used as a prognostic marker and may help identify those patients for whom early adjuvant treatment might be beneficial.     

Overexpression of cyclooxygenase-2 protein and its relationship to apoptosis in cervical carcinoma treated with neoadjuvant chemotherapy

The aims of this study were to examine the overexpression of COX-2 protein and its relationship to apoptosis in cervical carcinoma patients treated with neoadjuvant chemo-therapy (NAC), and to assess the potential role of COX-2 as a predictor of the response to NAC in a series of patients with cervical carcinoma. For immunohistochemical analysis, cervical cancer tissue samples were collected before NAC and 3 weeks after NAC using transcatheter arterial infusion of cisplatin from 40 patients who underwent surgery for advanced cervical carcinoma in stages IB, IIA and IIB and from 5 normal cervical tissues between 1991 and 2000 at the Department of Obstetrics and Gynecology, under informed consent. Patients were randomly assigned to receive one or two arterial infusions of cisplatin. COX-2 protein expression was detected by immunohistochemical staining and was classified as no expression for tumors with negative or <10%, while > or =10% positive staining was defined as overexpression. Detection of apoptosis was done by the TUNEL method. The percentage of cells with DNA fragmentation (apoptotic index, AI) was calculated before NAC and 3 weeks after NAC. The AI ratio (AI after NAC/AI before NAC) was also calculated. COX-2 expression was not detected in the normal cervix. Overexpression of COX-2 protein was detected in 18 out of 40 (45.0%) cervical cancers. A higher incidence of COX-2 protein overexpression was observed in patients with adenocarcinoma than in those with squamous cell carcinoma (p=0.1797, Fisher's exact text). The average AI value before and after NAC was 8.85 versus 11.82 respectively. In COX-2 protein-negative patients with squamous cell carcinoma, the AI ratio was 0.96+/-0.46 following one arterial infusion of cisplatin and 3.19+/-2.72 following two infusions of cisplatin. There was a significant positive correlation between apoptosis and the number of infusions of cisplatin (p=0.0098, Mann-Whitney, U-test). Our findings suggest that COX-2 protein expression could be used as a predictor of chemoresistance and that assessment of the COX-2 status could be useful to identify cervical cancer patients who may benefit from NAC.     

Mucoepidermoid carcinoma of the salivary gland--a clinico-pathologic and immunohistochemical study for c-erbB-2 oncoprotein.

Twenty-five cases of mucoepidermoid carcinoma of the salivary glands were studied with respect to clinico-pathologic features, prognostic factors, and c-erbB-2 oncoprotein expression. Fourteen cases were located in parotid glands, 2 in submandibular glands and 9 in minor salivary glands. Fourteen patients were confirmed to have local recurrences, 6 patients manifested systemic metastases, and 10 patients died of the disease. They were histologically graded as I in 5, II in 12 and III in 8 cases respectively, and the histologic grade was significantly correlated with disease-free interval and overall survival of the patients. c-erbB-2 overexpression was observed in 9 cases (36%), with a trend to be associated with the higher grade, but was not evaluated as a significant survival-related factor in this series. Larger size and major gland location of the tumors were correlated with more frequent regional lymph node metastases. The present study showed that c-erbB-2 overexpression was not uncommonly present in mucoepidermoid carcinoma of the salivary glands, especially of higher grade, and the histologic grade was the most important and handy prognostic indicator.     

Sebaceous carcinoma of the eyelids: frequent expression of c-erbB-2 oncoprotein

Ocular sebaceous carcinoma (OSC) is an uncommon malignancy with a potential to recur and metastasize. Some characteristics of sebaceous carcinoma, such as female preponderance, shown in the present series during 11-year period at Korea Cancer Center Hospital, led us to study their hormone receptors and c-erbB-2 expression. c-erbB-2 overexpression was very common (83%) in OSC, and was not associated with pathologic findings or clinical outcome. Interestingly, estrogen and progesterone receptor was detected in 4 and 2 cases, respectively, suggesting a role of hormonal influence on this neoplasm. Immunohistochemical and clinicopathologic features of 18 cases of OSC in Korea are presented.     

Correlation between laminin-5 immunohistochemistry and human papillomavirus status in squamous cervical carcinoma

BACKGROUND: Human papillomavirus (HPV) plays a critical role in the carcinogenesis of squamous cervical carcinoma. Integration of viral DNA into the host genome is a major contributing factor to malignant transformation. Viral load may influence integration. AIMS: To compare HPV status (type, viral load, integration status) between normal samples, carcinoma in situ and invasive carcinoma in order to elucidate the role of HPV in progression to invasive lesions. METHODS: The study population comprised 10 biopsy samples from each diagnostic group. Laminin-5 immunohistochemistry was performed to distinguish invasive carcinoma from non-invasive high-grade lesions. Real-time PCR was used to detect specific HPV types, viral load and integrated HPV, with quantification of viral E2 and E6 genes. RESULTS: Invasive carcinomas contained a higher number of laminin-5 immunoreactive cells as compared to non-invasive lesions. Almost all samples contained HPV, with a higher viral load and copy number of HPV16 integrated in E2 in cases of laminin-5 immunoreactivity and cases of invasive carcinoma. High HPV16 viral load was associated with more integrated copies in E2. CONCLUSIONS: HPV is important in progression from carcinoma in situ to invasive carcinoma. Viral load and HPV integration influence the development of cervical cancer towards invasiveness. Overall HPV status may be more predictive of patient outcome and may influence patient management.     

Expression of c-erbB-2 oncoprotein in mammary and extramammary Paget's disease.

Formalin-fixed, paraffin-embedded tissue sections from 45 patients with mammary and extramammary Paget's disease were stained immunohistochemically with the use of a polyclonal antiserum directed against a 14-amino acid segment of the c-erbB-2 oncoprotein. Positive membrane staining, which correlates with gene amplification, was found in 15 of 19 cases (79%) of mammary Paget's disease, 4 of 13 cases (31%) of vulvar Paget's disease, none of 8 cases of scrotal Paget's disease, and none of 5 cases of perianal Paget's disease. Of the 19 patients with mammary Paget's disease, specimens of underlying breast tissue were available from 14; all contained a concurrent ductal adenocarcinoma. Concordance of c-erbB-2 antigen staining between the underlying breast carcinoma and the pagetoid component was observed in 12 cases. Of the 13 patients with vulvar Paget's disease, 2 had superficial stromal invasion, and 3 had underlying, deeply invasive adenocarcinomas. One superficially invasive case was positive for c-erbB-2 expression. One additional case of vulvar Paget's disease had an associated primary pagetoid endocervical adenocarcinoma that spread into the endometrium; both the endocervical and vulvar components stained positively for the c-erbB-2 antigen. The results of this study indicate that the c-erbB-2 oncoprotein may play a role in the pathogenesis of extramammary Paget's disease. These results also suggest that the c-erbB-2 oncoprotein may function in vivo to promote intraepithelial spread of adenocarcinoma cells.     

Correlation between histological grade and c-erbB2 oncoprotein overexpression in infiltrating ductal carcinoma of breast

One hundred and twelve infiltrating ductal carcinoma of breast were studied by the standard avidinbiotin complex immunoperoxidase method on formalin-fixed, paraffin-embedded tissue sections, using a monoclonal antibody to c-erbB-2 oncoprotein. The same tumours were assessed and scored according to the Bloom and Richardson criteria into three histological grades. The distribution of tumours according to grade were: 8 Grade I, 34 Grade II and 70 Grade III. Forty-three (38.4%) tumours showed positive membrane staining for c-erbB-2 oncoprotein. These comprised 7 Grade II and 36 Grade III tumours with c-erbB-2 immunopositivity rates of 20.6% and 51.4% respectively. The oncoprotein was not expressed by Grade I tumours. This study shows a good correlation between c-erbB-2 expression and histological grade, a known prognostic indicator of invasive breast carcinoma. Because the c-erbB-2 oncogene has extensive structural homology to the epidermal growth factor receptor gene, its overexpression can be expected to result in more aggressive tumour behaviour. While it may be regarded as another indicator of poor prognosis breast cancers, its value in the selection of carcinomas less responsive to hormonal therapy and those more suitable for immunotherapy than chemotherapy has been mooted but remains to be clarified.     

Immunoelectron microscopical identification of the c-erbB-2 oncoprotein in patients with laryngeal squamous cell carcinoma

The peroxidase-antiperoxidase (PAP) method was used for localization of the c-erbB-2 oncoprotein at the electron microscopical level in 15 patients with laryngeal squamous cell carcinoma. It was found that c-erbB-2 oncoprotein was present in 7 of 15 samples. Electron microscopical examination revealed expression of the c-erbB-2 oncoprotein both on the membrane of individual cells and in the cytoplasm. In 5 of the 7 cases of positive labeling, it was observed only on the plasma membrane of cells whereas in 2 cases, there was also cytoplasmic staining. Reaction product was associated with endoplasmic reticulum, and the nuclear envelope and was scattered throughout the cytoplasm on ribosomes. Control incubations using normal rabbit serum instead of the primary antibody showed no labeling. A significant correlation between c-erbB-2 oncoprotein and pathological characteristics such as nodal status and histological grade was not found.     

食管癌细胞中c-erbB-2与P-gP表达的相关性

目的　探讨食管癌细胞c erbB 2与多药耐药性相关性及其临床意义。方法　用免疫组化方法检测癌细胞c erbB 2和用流式细胞术检测了 4 6例食管癌手术标本中癌细胞P 糖蛋白 (P gp)表达水平 ,并进行相关性分析。 结果　食管癌中c erbB 2表达阳性 12 / 4 6例 (2 6 1% ) ;P gp表达阳性 2 8/ 4 6例 (6 0 9% )。食管癌淋巴结转移情况与c erbB 2和P gp表达比较发现 ,在c erbB 2阳性时淋巴结有转移 (31 0 9%± 5 33% )与无转移 (8 0 4 %± 3 0 3% )组的P gp表达比较差异有显著性(P =0 0 0 73) ,而在c erbB 2阴性时淋巴结转移情况与P gp表达无相关性。食管癌临床分期与c erbB 2和P gp表达比较发现 ,在c erbB 2阳性时 ,Ⅲ～Ⅳ期 (33 6 8%± 5 5 1% )与Ⅱ期 (9 30 %± 2 78% )组P gp表达比较 ,差异有显著性 (P =0 0 0 2 7) ,而在c erbB 2阴性时临床分期与P gp表达无相关性。食管癌肿瘤大小、肿瘤分化程度与c erbB 2和P gp表达均无相关性。结论　在c erbB 2表达阳性时食管癌中有淋巴结转移、临床Ⅲ～Ⅳ期患者与P gp表达升高有相关性 ,提示双阳性时肿瘤患者预后较差。但在c erbB 2表达阴性时食管癌有淋巴结转移、临床分期与P gp表达无相关性     

EGFR family expression in breast carcinomas. c-erbB-2 and c-erbB-4 receptors have different effects on survival.

One hundred patients with breast carcinoma followed for 7-11 years were included in the present study of EGFR family members, using immunohistochemistry and RT-PCR. By immunohistochemistry, 36%, 27%, 26%, and 82% of the tumours were positive for EGFR, c-erbB-2, c-erbB-3, and c-erbB-4. All the immunoreactive tumours were confirmed positive by RT-PCR. Tumour size, histological grade, lymph node status, S-phase fraction, and stage were confirmed to be significantly associated with both disease-free and cancer-specific survival in the present study. Methods of treatment, histological type, and ploidy had no significant effect on survival. Statistical analysis of EGFR family members in these tumours showed a significant association between c-erbB-2 expression and reduced disease-free and cancer-specific survival. c-erbB-4 expression was associated with a more favourable outcome. Co-expression of c-erbB-2 and EGFR was associated with a worse prognosis. c-erbB-4 expression, however, showed an antagonistic effect on the clinical influence of c-erbB-2 expression. In conclusion, c-erbB-2 expression in breast carcinomas is associated with an unfavourable clinical course and EGFR expression has a synergistic effect. However, c-erbB-4 antagonizes the c-erbB-2 effect on clinical course in breast carcinomas. To achieve best results with immunotherapy against the c-erbB-2 receptor, clarifying the status of c-erbB-4 expression may be of significance.     

The predictive value of EGFR and HER-2/neu in tumor tissue and serum for response to anthracycline-based neoadjuvant chemotherapy of breast cancer

We investigated the predictive value of HER-2/neu and epidermal growth factor receptor (EGFR) in tumor tissue and prechemotherapy serum for histopathologic response in 108 patients with breast cancer undergoing neoadjuvant anthracycline-based chemotherapy.Response to chemotherapy, assessed by histopathologic classification of regression (grade 0 [no therapy effect] to 4 [no residual tumor]), correlated significantly with prechemotherapy serum HER-2/neu levels. Median prechemotherapy serum HER-2/neu levels were significantly higher in patients with regression grades 1 through 4 compared with those in patients with regression grade 0 (9.6 vs 8.55 ng/mL; P = .011; 95% confidence interval [CI], .009-.014). Median pretreatment serum HER-2/neu levels of patients with complete pathologic response (pCR) were significantly higher than in patients with moderate or no treatment response (10.95 vs 9.1 ng/mL; P = .041; 95% CI, .036-.046). Receiver operating characteristic curve analysis revealed a serum HER-2/neu value of more than 10.3 ng/mL to predict a pCR with 80% sensitivity and 69.4% specificity. There was no significant correlation of response with HER-2/neu and EGFR scores in tumor tissue or with serum EGFR levels.Results demonstrate prechemotherapy serum HER-2/neu to be a significant predictor of response to neoadjuvant anthracycline-based chemotherapy for breast cancer.     

乳腺癌新辅助化疗后临床评价与病理评价的差异分析

目的 探讨乳腺癌新辅助化疗后,临床疗效评价与病理评价之间存在差异的病理学基础.方法 收集中国医学科学院肿瘤医院2005年6月至2007年12月施行乳腺癌新辅助化疗的209例.新辅助化疗前均行核芯针穿刺活检.化疗结束后4周内实施乳腺癌根治术.新辅助化疗前后均对乳腺原发灶进行临床体检、乳腺X线检查和(或)超声检查.实施新辅助化疗后,依实体瘤的疗效评价标准(RECIST,1.1版)对乳腺癌原发灶进行临床疗效评价,依Miller和Payne(MP)分级系统进行病理评价.应用SPSS 15.0软件分析临床评价与病理评价的相关性.结果 (1)新辅助化疗后依临床体检结果进行临床评价:完全缓解33例,部分缓解124例,疾病稳定41例,疾病进展11例.(2)新辅助化疗前后均行乳腺X线检查87例,依乳腺X线检查进行临床评价:完全缓解8例,部分缓解42例,疾病稳定37例.(3)新辅助化疗后MP分级病理评价:1级14例,2级35例,3级106例,4级36例,5级18例.(4)临床体检相关的临床评价与病理评价存在统计学相关性(x2=33.668,P=0.001),乳腺X线检查相关的临床评价与病理评价存在统计学相关性(x2=22.404,P=0.004).(5)新辅助化疗病理评价与X线检查相关临床评价存在差异的病理学改变有:残存浸润癌以脉管瘤栓为主要表现形式;伴有大片黏液湖形成的黏液腺癌;导管内癌残存,伴明显沙砾样钙化及周围组织的沙砾样钙化;间质结节状纤维化等.结论 乳腺癌新辅助化疗的临床评价与病理评价存在统计学相关性.两者之间的差异有相应的病理学基础.伴有大片黏液湖形成的黏液腺癌、导管内癌的残存伴沙砾样钙化及间质结节状纤维化可能是临床评价低估治疗疗效的原因之一;而残存癌表现为脉管瘤栓可能是临床评价高估治疗疗效的原因之一.     

乳腺癌新辅助化疗后临床评价与病理评价的差异分析

目的 探讨乳腺癌新辅助化疗后,临床疗效评价与病理评价之间存在差异的病理学基础.方法 收集中国医学科学院肿瘤医院2005年6月至2007年12月施行乳腺癌新辅助化疗的209例.新辅助化疗前均行核芯针穿刺活检.化疗结束后4周内实施乳腺癌根治术.新辅助化疗前后均对乳腺原发灶进行临床体检、乳腺X线检查和(或)超声检查.实施新辅助化疗后,依实体瘤的疗效评价标准(RECIST,1.1版)对乳腺癌原发灶进行临床疗效评价,依Miller和Payne(MP)分级系统进行病理评价.应用SPSS 15.0软件分析临床评价与病理评价的相关性.结果 (1)新辅助化疗后依临床体检结果进行临床评价:完全缓解33例,部分缓解124例,疾病稳定41例,疾病进展11例.(2)新辅助化疗前后均行乳腺X线检查87例,依乳腺X线检查进行临床评价:完全缓解8例,部分缓解42例,疾病稳定37例.(3)新辅助化疗后MP分级病理评价:1级14例,2级35例,3级106例,4级36例,5级18例.(4)临床体检相关的临床评价与病理评价存在统计学相关性(x2=33.668,P=0.001),乳腺X线检查相关的临床评价与病理评价存在统计学相关性(x2=22.404,P=0.004).(5)新辅助化疗病理评价与X线检查相关临床评价存在差异的病理学改变有:残存浸润癌以脉管瘤栓为主要表现形式;伴有大片黏液湖形成的黏液腺癌;导管内癌残存,伴明显沙砾样钙化及周围组织的沙砾样钙化;间质结节状纤维化等.结论 乳腺癌新辅助化疗的临床评价与病理评价存在统计学相关性.两者之间的差异有相应的病理学基础.伴有大片黏液湖形成的黏液腺癌、导管内癌的残存伴沙砾样钙化及间质结节状纤维化可能是临床评价低估治疗疗效的原因之一;而残存癌表现为脉管瘤栓可能是临床评价高估治疗疗效的原因之一.     

Expression of c-erbB-2 oncoprotein in salivary gland tumours: an immunohistochemical study.

Sections of formalin-fixed, paraffin-embedded primary salivary gland tumours were stained with a monoclonal antibody to the c-erbB-2 oncoprotein to determine the incidence and significance of expression of this protein. The series of 131 tumours comprised 33 cases of pleomorphic adenoma, 2 of malignant mixed tumour, 1 oxyphil adenoma, 31 Warthin's tumours, 4 basal cell adenomas, 6 mucoepidermoid carcinomas, 14 acinic cell carcinomas, 19 adenoid cystic carcinomas, 3 squamous carcinomas, and 18 poorly differentiated adenocarcinomas. Positive staining, as defined in previous studies, was present in five tumours (three cases of poorly differentiated adenocarcinoma, one mucoepidermoid carcinoma, and one adenoid cystic carcinoma). A review of the medical records of all patients did not disclose any clear difference between the clinical behaviour of positive and negative cases over a period of follow-up that ranged from 18 to 120 months. The findings of this study indicate that the protein product of the c-erbB-2 proto-oncogene is infrequently expressed in salivary gland tumours, and when it is localized on the tumour cell surface membrane, there is no clear evidence that this determines the biological behaviour of the tumour.     

乳腺癌新辅助化疗组织学疗效评价研究

目的 探讨乳腺癌新辅助化疗后根治标本的组织学疗效评价标准.方法 收集2005年6月至2007年6月乳腺癌新辅助化疗154例档案,其中改良根治术139例,保乳手术15例.化疗结束后4周内实施乳腺根治术.按照Miller and Payne(MP)分级系统的标准规范进行取材、制片和按该系统组织学疗效评价标准进行分级评价,同时与既往应用的肿瘤治疗反应评价系统(既往评价系统)进行比较.对所有病例进行常规随访.应用SPSS 13.0软件进行统计学处理.结果 (1)154例手术标本所获得的组织学疗效评价信息:MP分级系统1级12例(7.8%)、2级33例(21.4%)、3级64例(41.6%)、4级31例(20.1%)、5级14例(9.1%);既往评价系统分别为轻度治疗反应51例(33.1%)、中度治疗反应71例(46.1%)、重度治疗反应32例(20.8%).MP分级系统与既往评价系统各组病例比例之间存在统计学相关(X2=186.660,P<0.01).(2)154例患者中147例获得随访信息(95.5%),随访时间16～38个月;其中14例出现术后复发、远处转移或死亡.MP分级系统5个级别组与患者生存状态均相关(X2=11.612,P=0.020),既往评价系统3个级别组与患者生存状态均无关(X2=0.881,P=0.644).结论 MP分级系统可以用于肿瘤化疗后的组织学疗效评价,与预后相关.