卵巢子宫内膜样癌HER－2／neu的表达

目的研究卵巢子宫内膜样癌ＨＥＲ－２／ｎｅｕ的表达以及与临床病理特征和预后的关系。方法应用ＨＥＲ－２／ｎｅｕ单克隆抗体免疫组化技术对卵巢子宫内膜样癌２８例进行ＨＥＲ－２／ｎｅｕ癌基因蛋白测定。结果１３例细胞浆染色阳性，占４６．４％，Ⅰ期肿瘤阳性率为２０．０％，Ⅱ～Ⅳ期肿瘤阳性率为５２．２％，手术有残留肿瘤者ＨＥＲ－２／ｎｅｕ的表达率是６２．５％，无残留肿瘤者ＨＥＲ－２／ｎｅｕ表达率是２５．０％，差异有显著性（Ｐ＝０．０４９）。ＨＥＲ－２／ｎｅｕ表达与发病年龄、ＣＡ１２５水平、组织学分级及淋巴转移无关。术后随诊６～９６个月，平均３１．３个月，ＨＥＲ－２／ｎｅｕ阳性者术后死亡率是３８．５％，ＨＥＲ－２／ｎｅｕ阴性者术后死亡率是２１．４％。结论ＨＥＲ－２／ｎｅｕ阳性者与卵巢子宫内膜样癌的不良预后有一定的关系。     

HER-2/neu及细胞角蛋白在卵巢上皮性肿瘤原发灶和转移灶中表达的检测及临床意义的研究

目的：了解卵巢上皮性肿瘤原发灶和转移灶中癌基因ＨＥＲ－２／ｎｅｕ和细胞角蛋白表达状况及其临床意义。方法：用免疫组化法检测卵巢上皮肿瘤原发灶６９份及转移灶３８份（５１处）标本中ＨＥＲ－２／ｎｅｕ和细胞角蛋白的表达，并与术后组织学分级及患者生存期分析相结合。结果：原发灶中二者阳性表达率与术后患者生存期无相关性（Ｐ＞０．０５）。角蛋白与组织学分级有关（Ｐ＜０．０５），而且在转移灶癌细胞中表达较稳定。在转移灶中ＨＥＲ－２／ｎｅｕ的表达明显低于原发灶中者（Ｐ＜０．０５），在原发灶和转移灶中都呈阳性表达的患者预后较差（Ｐ＜０．０５）。结论：在卵巢上皮性肿瘤原发灶和转移灶中ＨＥＲ－２／ｎｅｕ的表达有显著差别，其原因有待进一步研究。原发灶和转移灶中ＨＥＲ－２／ｎｅｕ都表达的患者提示预后不良。角蛋白与卵巢上皮性肿瘤分化程度有关，在转移灶中表达较稳定     

HER—2／neu及细胞角蛋白在卵巢上皮性肿瘤原发灶和转移灶中表 …

目的：了解卵巢上皮性肿瘤瘤原发灶和转移灶中癌基因ＨＥＲ－２／ｎｅｕ和细胞角蛋白表达状况及其临床意义，方法：用免疫组化法检测卵巢上皮肿瘤原发性灶６９份及转移灶３８份（５１处）标本中ＨＥＲ－２／ｎｅｕ和细胞角蛋白的表达，并与术后组织学分级及患者生存期分析相结合，结果：原发灶中二者阳性表达率与术后患者生存期无相关性（Ｐ〉０．０５）。角蛋白与组织学分级有关（Ｐ〈０．０５），而且在转移灶癌细胞中表达的稳定。     

子宫内膜癌bcl-2癌基因的持续性表达及其临床意义

目的：研究子宫内膜癌ｂｃｌ－２癌基因的表达及其临床意义。方法：采用免疫组化ＡＢＣ法检测增生期、分泌期、单纯型增生、复合型增生及不典型增生子宫内膜共２６份，子宫内膜癌４９例的ｂｃｌ－２癌基因蛋白表达及雌、孕激素受体（ＥＲ、ＰＲ）的表达。结果：正常增生期子宫内膜、增生的子宫内膜存在ｂｃｌ－２的表达，与ＥＲ相关，分泌期子宫内膜ｂｃｌ－２表达下降；４９例子宫内膜癌中２６例ｂｃｌ－２表达阳性，占５３％，２９例ＥＲ表达阳性，占５９％，２５例ＰＲ表达阳性，占５１％。７２％ｂｃｌ－２表达阳性者ＥＲ阳性，７５％ｂｃｌ－２表达阴性者ＥＲ阴性（Ｐ＜０．０１）。６８％ｂｃｌ－２表达阳性者ＰＲ阳性，６２％ｂｃｌ－２阴性者ＰＲ阴性（Ｐ＜０．０５）。子宫内膜癌Ｇ１、Ｇ２级ｂｃｌ－２的表达率为６６％，显著高于Ｇ３级者（２１％）（Ｐ＜０．０５）。ｂｃｌ－２的表达与肌层浸润、手术分期无关，ｂｃｌ－２表达阳性及阴性者生存率统计差异无显著性。结论：子宫内膜ｂｃｌ－２的持续性表达与卵巢激素相互作用可能在子宫内膜癌发生、发展中起作用     

子宫内膜癌ras及HER—2／neu癌基因的表达

子宫内膜癌ｒａｓ及ＨＥＲ－２／ｎｅｕ癌基因的表达薛凤霞焦书竹王海燕陈斌其为探讨ｒａｓ、ＨＥＲ－２／ｎｅｕ癌基因与子宫内膜癌临床及病理学特征的关系，本研究检测了１０３例子宫内膜癌组织中ｒａｓ、ＨＥＲ－２／ｎｅｕ癌基因的表达情况。一、材料和方法：１．临床...     

卵巢上皮性肿瘤雌孕激素受体的单克隆抗体免疫组化研究

利用抗雌激素受体（ＥＲ）和孕激素受体（ＰＲ）的两种单克隆抗体对３１例卵巢上皮性肿瘤新鲜冰冻标本进行ＡＢＣ法测定，ＥＲ、ＰＲ的阳性表达率分别为４５．２％和４８．４％，恶性肿瘤ＥＲ的含量高于良性者，ＰＲ在良、恶性肿瘤间未见有明显差异。提示：部分卵巢上皮性肿瘤属于激素依赖性肿瘤，对晚期卵巢癌可试用激素疗法。ＥＲ、ＰＲ在宫内膜样癌和浆液性癌的含量高于其它类型上皮性肿瘤，高分化者受体阳性率及含量高于低分化者；ＥＲ或ＰＲＦ阳性者预后好于阴性者，二者具独立的预后因素，且ＥＲ、ＰＲ双阳性者预后比ＥＲ阳性、ＰＲ阴性或ＥＲ阴性、ＰＲ阳性者好。     

错配修基因hMSH2蛋白在人卵巢恶性肿瘤组织中的表达及其临 …

目的 检测ｈＭＳＨ２基因在人卵巢恶性肿瘤组织中的表达及其与卵巢恶性肿瘤临床病理特征的关系。方法 应用免疫组织化学链酶菌抗生物素蛋白－过氧化物酶连接检测４２例卵巢恶性肿瘤组织中错配修复基因ｈＭＳＨ２蛋白的表达。结果 ２６例卵巢恶性肿瘤组织有ｈＭＳＨ２蛋白表达（６２％）,多发生于浆液性腺癌和粘液性腺癌（８０％的８０％）,而在子宫内膜样癌和恶性生殖细胞肿瘤中表达较少（１／６和１／６,Ｐ〈０．０５）,其中     

c—erbB2在增生性和恶性子宫内膜组织中的扩增与表达

目的：探讨子宫内膜癌的发生及发展与癌基因ｃ－ｅｒｂＢ２表达的关系。方法：应用差别聚合酶链反应（ＤＰＣＲ０和免疫组化法测定了２５例正常子宫内膜、３１例增生性子宫内膜和７２例子宫内膜癌组织中癌基因ｃ－ｅｒｂＢ２的扩增与表达。结果：正常子宫内膜仅２例（２／２５，８．０％）低倍扩增，而子宫内膜增生及内膜癌组织中分别有１５和４５例（１５／３１，４８．４％；４５／７２，６２．５％）扩增，且扩增倍数从２－１２不     

癌基因HER－2／neu在良性、交界性和恶性上皮性卵巢肿瘤中的表达

癌基因ＨＥＲ－２／ｎｅｕ在良性、交界性和恶性上皮性卵巢肿瘤中的表达陶光实张志胜黄锦张琼英目前，有关ｎｅｕ基因与卵巢癌的关系尚未完全清楚。本研究采用癌基因产物ｃ－ｎｅｕ（Ａｂ－３）单抗及免疫组化ＡＢＣ法，检测正常卵巢、卵巢良性、交界性、恶性上皮性肿瘤ｎ...     

c－erbB2在增生性和恶性子宫内膜组织中的扩增与表达

目的：探讨子宫内膜癌的发生及发展与癌基因ｃ－ｅｒｂＢ２表达的关系。方法：应用差别聚合酶链反应（ＤＰＣＲ）和免疫组化法测定了２５例正常子宫内膜、３１例增生性子宫内膜和７２例子宫内膜癌组织中癌基因ｃ－ｅｒｂＢ２的扩增与表达。结果：正常子宫内膜仅有２例（２／２５，８．０％）低倍扩增，而子宫内膜增生及内膜癌组织中分别有１５和４５例（１５／３１，４８．４％；４５／７２，６２．５％）扩增，且扩增倍数从２～１２不等。免疫组化与ＤＰＣＲ法测定结果在阴性标本有很好的相关性。在子宫内膜增生中，不典型增生与复合增生的扩增率明显高于单纯性增生者。子宫内膜癌中，ｃ－ｅｒｂＢ２的高倍扩增率（≥５倍）与肿瘤的病理分级和癌细胞对血管或淋巴管侵入密切相关。结论：子宫内膜增生的癌变可能与ｃ－ｅｒｂＢ２的激活有关。高度激活的ｃ－ｅｒｂＢ２与内膜癌的发展、分化以及转移倾向密切相关，有可能作为临床预后的指标之一。     

Effect of HER-2/neu overexpression on chemoresistance and prognosis in ovarian carcinoma

AIM: To investigate the effect of HER-2/neu protein overexpression on chemoresistance and prognosis in patients with epithelial ovarian carcinoma. METHODS: A total of 141 ovarian carcinoma tissues surgically resected between 1987 and 2003 were assessed by immunohistochemistry (IHC). The characteristic of the patients and immunohistochemical results were compared by chi2-test. Survival analysis was performed by the Kaplan-Meier method and the log-rank test. RESULTS: HER-2/neu overexpression was detected in 18 cases (12.8%). There were no significant differences in histopathological subtypes (P = 0.3550), FIGO stages (P = 0.8858), or residual tumor size at first surgery (P = 0.6607) between the cases with HER-2/neu overexpression and the cases without HER-2/neu overexpression. Among the 58 cases which responded to chemotherapy, only five cases (8.6%) showed HER-2/neu overexpression. However, among the 38 cases which did not respond to chemotherapy, eight cases (21.1%) showed HER-2/neu overexpression. Overexpression of HER-2/neu had a tendency to relate with chemoresistance of epithelial ovarian carcinoma, but there were no statistically significant differences (P = 0.0817). No association was observed between HER-2/neu overexpression and cumulative survival rate (P = 0.4970). CONCLUSIONS: The results of the current study show that although HER-2/neu overexpression has a tendency to be associated with chemoresistance, it can not be a prognostic factor for the patients with epithelial ovarian carcinoma.     

HER-2/neu amplification and overexpression in endometrial carcinoma.

HER-2/neu is a proto-oncogene associated with poor prognosis in women with breast and ovarian carcinoma. The significance of HER-2/neu in endometrial carcinoma is less clearly established. The authors compared HER-2/neu gene amplification using fluorescence in situ hybridization and protein overexpression using immunohistochemistry with survival in patients with endometrial carcinoma. Fluorescence in situ hybridization and immunohistochemical staining were performed on 72 formalin-fixed, paraffin-embedded endometrial carcinoma specimens. Vysis combination HER-2/neu and centromere 17 probe mixture was applied to isolated tumor cell nuclei. A minimum of 200 nuclei were scored for each specimen using standard signal enumeration criteria. A specimen was considered amplified with 5% or greater amplified nuclei. Tissue sections were immunostained with polyclonal antibody against p185erb-2 transmembrane glycoprotein. Immunohistochemical reactivity was scored on a three-tiered scale. HER-2/neu gene amplification and protein overexpression were detected in 15 of 72 (21%) and 12 of 72 (17%) of the specimens, respectively, with 2 cases of normal copy overexpression and 5 cases of amplification without overexpression. Both amplification and overexpression were associated with higher grade tumors. Amplification was associated with clear cell and serous subtypes (p = 0.002), and overexpression with only clear cell type (p = 0.006). Using the proportional hazards model of survival, amplification was found to have significant negative predictive value beyond stage, grade, and cell type (p = 0.002). HER-2/neu gene amplification as detected by fluorescence in situ hybridization in archival material has significant prognostic value.     

Overexpression/amplification of HER-2/neu is uncommon in invasive carcinoma of the uterine cervix.

The aim of this study was to investigate HER-2/neu (c-erbB2) overexpression/amplification in carcinoma of the uterine cervix using immunohistochemistry and fluorescent in situ hybridization (FISH) to assess whether anti-p185c-erbB2 therapy might have potential benefits in patients with advanced invasive cervical carcinoma. The authors used a protocol for p185c-erbB2 immunohistochemistry (clone CB11) that has been previously calibrated using FISH as the gold standard, showing a 98% accuracy rate in a large series of breast carcinomas. Immunolabeling for p185c-erbB2 was present in 24 of 82 (29%) of the tumors, but only 2 tumors (2%) with a labeling of more than 60% of the cells were considered positive for overexpression. FISH analysis did not find HER-2/neu gene amplification in these cases, although five other tumors showed weak and/or focal immunolabeling. There was no correlation between the presence of immunolabeling and age, histologic type, or clinical stage. Overexpression/amplification of HER-2/neu is uncommon in invasive cervical carcinoma, suggesting that there is little indication for using anti-p185c-erbB2 therapy in the treatment of these patients.     

Overexpression of HER-2/neu is not a risk factor in ovarian clear cell adenocarcinoma

OBJECTIVE: To evaluate the significance of the expression of HER-2/neu as a prognostic factor, we retrospectively examined its overexpression rates chiefly in ovarian clear cell adenocarcinoma (CCA) and their relationships with FIGO stage, lymph node metastasis, and prognosis. METHODS: In addition to 90 specimens of CCA (stage I, 52; stage II, 7; stage III, 28; stage IV, 3) obtained between 1987 and 2002, 19 specimens of serous adenocarcinoma (S), 19 specimens of mucinous adenocarcinoma (M), and 19 specimens of endometrioid adenocarcinoma (E) collected at initial surgery were studied. The expression of HER-2/neu was immunohistologically scored on a scale of 0 to 3+ according to the HercepTest scoring system, and 2+ and 3+ were regarded as overexpression. The relationship between HER-2/neu overexpression and outcome was evaluated by the Kaplan-Meier method and the log-rank test. The relationship with advanced-stage cancer was analyzed by Fisher's exact test. The relationships with lymph node metastasis and histologic types were compared by the t test. RESULTS: The rate of HER-2/neu overexpression in CCA was 45.6% (0, 1+, 2+, and 3+ in 14, 35, 36, and 5 cases, respectively), and no differences in the overexpression rate were noted among histologic types: 52.7% in S, 42.1% in M, and 26.4% in E. In CCA, no association was observed between HER-2/neu overexpression and cumulative survival rate (P = 0.5708), FIGO stage (P = 0.5147), or lymph node metastasis (P = 0.3624). CONCLUSION: The absence in CCA of an association between HER-2/neu overexpression and outcome, stage, or lymph node metastasis indicates that HER-2/neu overexpression is not a prognostic risk factor.     

Borderline tumors of the ovary: a clinico-pathologic and immunohistochemical study of 54 cases

OBJECTIVE: To study EGF-R, HER-2/neu (p185), p53, Mib-1 (Ki-67), Bax, Bcl-2, ras expression and ploidy in borderline tumors of the ovary by assessing their frequency, and relationship to histologic type, tumor recurrence and survival. METHODS: Fifty-four patients with borderline tumors were followed 3-140 months (median: 38 months). Paraffin-embedded sections were stained using monoclonal antibodies against EGF-R, HER-2/neu (p185), p53, Mib-1 (Ki-67), Bax, Bcl-2, and ras. The immunohistochemical findings were correlated to histologic subtype, tumor recurrence, and survival. RESULTS: Positivity for EGF-R was found in 24% (13/54), in 22% (12/54) p185 was positive, 9% (5/54) of tumors were p53-positive, Mib-1 (Ki-67)-positivity was demonstrable in 46% (25/54). Expression of Bax, Bcl-2, and ras was found in 37% (20/54), 28% (15/54) and in 7% (4/54) of the cases, respectively. CONCLUSION: The data demonstrate expression of EGF-R, p185/HER-2/neu, p53, Mib-1 (Ki-67), Bax, Bcl-2, and ras in a subgroup of patients with ovarian borderline tumors. Further studies to evaluate their prognostic value are warranted.     

The growth factor receptors HER-2/neu and EGFR, their relationship, and their effects on the prognosis in early stage (FIGO I-II) epithelial ovarian carcinoma

Abstract. Skirnisdóttir I, Sorbe B, Seidal T. The growth factor receptors HER-2/neu and EGFR, their relationship, and their effects on the prognosis in early stage (FIGO I–II) epithelial ovarian carcinoma.
Epithelial ovarian cancer is a heterogeneous disease and many biologic and molecular factors are important for its development and progression, including growth rate, metastatic potential, chemo- and radiosensitivity, and prognosis. Even in the early stages (FIGO I–II), many questions persist about the biologic behavior, optimal treatment, and prognosis.
In a series of 106 patients with epithelial ovarian cancers in FIGO stages IA-IIC, a number of known prognostic factors (age, FIGO stage, histopathologic type, and tumor grade) were studied in relation to two important growth factor receptors for oncogenesis (HER-2/neu and EGFR). Immunohistochemical techniques were used. All patients received adjuvant radiotherapy 4–6 weeks after the primary surgery. In a univariate analysis, the expression of the HER-2/neu receptor was not associated with any of the clinicopathologic factors studied or survival status. Positive EGFR staining was associated with poor survival in a univariate analysis. Co-expression of HER-2/neu and EGFR was most frequently seen in serous tumors and positive staining for HER-2/neu alone was associated with mucinous tumors. Both endometrioid and clear cell tumors belonged to the largest subgroup with concomitant negativity for both HER-2/neu and EGFR. In a multivariate Cox analysis, the tumor grade and EGFR status of the tumors were independent and significant prognostic factors. A therapeutic strategy for epithelial ovarian cancer might be to decrease EGFR expression by gene therapy in combination with adjuvant radiotherapy or chemotherapy.     

The prognostic and predictive value of immunohistochemically detected HER-2/neu overexpression in 361 patients with ovarian cancer: a multicenter study

OBJECTIVE: The prognostic and predictive relevance of HER-2/neu dysregulation in epithelial ovarian cancer is controversial. The purpose of our study was to document HER-2/neu expression patterns and their correlation with clinicopathologic parameters and survival in a large and biologically homogenous Caucasian patient collective. METHODS: Expression of HER-2/neu in ovarian cancer tissue was assessed by immunohistochemistry. Immunohistochemical staining was performed according to established protocols. Results were correlated to clinical data. RESULTS: HER-2/neu overexpression was detected in 6.9% (25/361) of the tumor samples and was significantly associated with tumor stage (P = 0.03), but not with lymph node involvement (P = 0.5), tumor grade (P = 0.3), histological type (P = 0.6), residual tumor (P = 0.4), serum CA-125 before therapy (P = 0.2), and patient age (P = 0.8). We found no significant influence of HER-2/neu overexpression on overall and disease-free survival independent of FIGO stage, tumor grade, and residual tumor mass. In a subset of 73 suboptimally debulked patients, women with response to first-line chemotherapy (complete remission [CR] + partial remission [PR]) and no response to first-line chemotherapy (stable disease [SD] + progressive disease [PD]) showed significantly different rates of HER-2/neu overexpression (0% [0/51] vs. 14% [3/22]; P = 0.02). CONCLUSIONS: Tumor overexpression of HER-2/neu in women with advanced ovarian cancer is rare and provides no prognostic information in addition to that provided by established clinicopathologic parameters. This multicenter study, however, indicates that HER-2/neu overexpression is a predictive factor for the response to first-line chemotherapy in suboptimally debulked patients.     

Comparative immunohistochemical study of endometrioid and serous papillary carcinoma of endometrium.

OBJECTIVE: The aim of this study was to determine whether immunohistochemical analysis of molecular parameters can provide an alternative method for classification of endometrial cancer cases according to their aggressiveness. METHODS: Sixty-four cases of endometrial carcinoma were assigned to three groups: group I--28 cases of endometrioid well and moderately differentiated (G1-G2) carcinoma; group II--14 cases of endometrioid poorly differentiated (G3) carcinoma; group III--22 cases of serous papillary endometrial cancer. Immunohistochemistry was used to determine the existence of estrogen receptors (ER), progesterone receptors (PR), and the expression of bcl-2, p53, HER-2/neu and Ki-67. RESULTS: There was a significant difference in the immunohistochemical profile of the studied molecular parameters comparing the three study groups. The endometrioid G1-G2 cases (group I) were characterized by increased immunoreactivity for ER and PR (85.7% and 78.6%, respectively), increased immunoreactivity for bcl-2 (42.8%) and low expression of p53 (14.3%) and HER-2/neu (14.3%). In contrast to group I cases, the serous papillary endometrial cancer cases (group III) were characterized by immunonegativity for ER, PR and bcl-2 and high immunoreactivity for p53 (81.8%) and HER-2/neu (45.4%). The endometrioid G3 cases (group II) demonstrated an intermediate immunoprofile, characterized by immunonegativity for ER, PR and HER-2/neu, low immunoreactivity for bcl-2 (7.1%) and high expression of p53 (57.1%). The expression of Ki-67 did not differ significantly comparing the different cases of endometrial cancer. CONCLUSION: This study provides evidence that the immunohistochemical analysis of endometrial carcinoma differentiates between different grades and histological types, thus being useful in the distinction of high risk cases.     

HER-2/neu overexpression in uterine papillary serous cancers and its possible therapeutic implications

Uterine papillary serous carcinoma (UPSC) is a highly aggressive variant of endometrial cancer with features similar to high-grade ovarian cancer. Patients tend to be elderly, thin, have a high grade tumor with extensive extrauterine disease at the time of diagnosis. The transmembrane receptor encoded by the HER-2 cellular oncogene is amplified in several types of human carcinomas and provides an attractive therapeutic target. HER-2/neu, the transmembrane receptor encoded by the c-erbB2 gene, is overexpressed by immunohistochemistry in <25% of ovarian cancers and 20-30% of breast cancers, and <10% of endometrial cancer. There are prognostic and therapeutic implications associated with the overexpression of this transmembrane protein. Herceptin, a humanized murine monoclonal antibody directed against the extracellular domain of the HER-2/neu protein, is being used to treat breast cancer that overexpresses HER-2/neu. We reviewed all patients diagnosed with UPSC between 1999-2001. Twenty-six patients were identified, and 19 patients had specimens available for evaluation. We performed immunohistochemical analysis (Herceptest, Dako, Carpinteria, CA) on 19 paraffin embedded blocks of UPSC tumors looking for HER-2/neu over expression. Five out of 19 (26%) stained heavily (3+) for HER-2/neu receptor protein. Four of these five patients had advanced disease at diagnosis. Two of these patients were subsequently treated with Herceptin; one with complete response and one with stable disease based on CT scan and CA-125 findings. Targeting HER-2/neu may be beneficial for a select group of patients with UPSC. We are continuing to evaluate samples for HER-2/neu over expression by fluorescence in situ hybridization (FISH).