Cyclooxygenase-2 expression in borderline ovarian tumors

OBJECTIVES: The aim of the study was to investigate by immunohistochemistry the expression of cyclooxygenase-2 (COX-2) in a single institutional series of borderline ovarian tumors (BOT). Moreover, to perform a comparative analysis, COX-2 expression was also analyzed in benign and malignant ovarian tumors. METHODS: Paraffin-embedded sections form 51 BOT, 26 benign, and 37 malignant ovarian tumors were incubated with polyclonal antiserum against COX-2. The results were calculated as the product of the percentage of the immunostained tumor cells by the relative staining score. Cases with immunostaining values of >1 were considered COX-2-positive. RESULTS: Thirty-four (66.7%) of fifty-one BOT were considered as COX-2-positive, and this rate was not significantly different with respect to COX-2 positivity in benign (50.0%) and in malignant (51.3%) ovarian tumors (P value = 0.23). A significantly higher percentage of COX-2 positivity was found in serous (24 of 24, 100%) with respect to mucinous (9 of 26, 34.6%) BOT (P value = 0.0001). Moreover, 7 (63.6%) of 11 endocervical-type mucinous borderline ovarian tumors were COX-2-positive with respect to only 2 of 15 (13.3%) intestinal-type mucinous BOT (P value = 0.013). The same trend was observed in benign lesions, with COX-2 positivity in 9 of 11 (81.8%) of serous versus 4 of 15 (26.7%) of mucinous tumors (P value = 0.015). On the other hand, no difference was found in the percentage of COX-2 positivity in serous (14 of 29, 48.3%) versus mucinous (5 of 8, 62.5%) ovarian carcinomas (P value = 0.22). CONCLUSIONS: COX-2 is differently expressed in BOT according to different histotype. Moreover, an increase of COX-2 positivity was observed from mucinous intestinal BOT to frankly malignant ovarian tumors suggesting that COX-2 overexpression might be involved in mucinous ovarian carcinogenesis.     

p63 expression in epithelial ovarian tumors

Ovarian cancer is a highly lethal disease and its underlying biology is poorly understood. The p63 is a homologue gene of the tumor suppressor p53. p63 appears to be important for the development and differentiation of reproductive epithelium and interacts with p53 in human tumorigenesis. This study presents the immunoexpression of the p63 in benign and malignant epithelial ovarian tumors. We evaluated the p63 immunoexpression in 91 ovarian benign cystadenomas (29 mucinous and 62 serous) and in 29 ovarian malignant tumors (3 mucinous borderline, 3 serous borderline, 17 serous carcinomas, 2 endometrioid, 2 undifferentiated, 1 mucinous, and 1 clear-cell carcinoma) using a monoclonal antibody clone 4A4 (1:200), which recognizes all p63 variants. The tumors were considered p63 positive if 5% or more cells presented nuclear immunostaining. We observed 85.7% of positivity in benign tumors, 50% in borderline tumors, and 8.7% in invasive ovarian cancer (P < .0001). The benign serous cystadenomas were positive in 91.9% of cases and benign mucinous cystadenomas in 72.4% (P= .02). These data suggests an important role of p63 in the control of ovarian epithelium behavior. The p63 may be involved in the development of benign and malignant epithelial ovarian tumors.     

Proliferating cell nuclear antigen (PCNA) immunoreactivity in ovarian serous and mucinous neoplasms: diagnostic and prognostic value

Sixty-two serous and mucinous ovarian tumors, an admixture of benign, borderline and malignant neoplasms, were immunostained for proliferating cell nuclear antigen (PCNA), with the monoclonal antibody PC10. The PC10 index, the proportion of cells showing nuclear positive staining, was calculated in each case. All the tumors showed positive immunoreactivity for PCNA. There was no overlap of PC10 counts between benign, borderline and malignant serous tumors but within the mucinous group of neoplasms there was considerable overlap between the counts for borderline and malignant tumors. There was no relationship between the PC10 index and the surgical stage of the malignant neoplasms and the index could not be correlated with patient death. Staining for PCNA does not, therefore, appear to be of any prognostic value in ovarian adenocarcinomas.     

Relationship between p53-associated proteins and estrogen receptor status in ovarian serous neoplasms

We studied the immunoexpression of p14ARF, MDM2, and p53, in addition to relationships between those protein expressions and estrogen receptor (ER)alpha in ovarian serous tumors including benign (n= 23), borderline (n= 41), and malignant (n= 94). The aberrant expressions of p14ARF, MDM2, and p53 were observed in 19.6% (31/158), 47.5% (75/158), and 39.9% (63/158) of cases, respectively. The expression of MDM2 was significantly higher in borderline tumors compared to benign (P= 0.04) and malignant (P < 0.01) tumors. p53 expression in borderline tumors was uncommon, and p14ARF expression loss was mainly observed in carcinomas. Altered expression of p14ARF, MDM2, and p53 shows significant relationship with stage. Overexpression of MDM2 (P= 0.01) and loss of p14ARF expression (P= 0.04) were significantly associated with ER expression. Our results suggest that alteration of p14ARF-MDM2-p53 pathway proteins may contribute significantly to the tumorigenesis of ovarian serous neoplasms, and ER is involved in cellular regulation of p14ARF-MDM2-p53 pathway in ovarian serous neoplasms.     

Periodic acid-Schiff stain as a prognostic indicator in serous and mucinous ovarian tumors

The prognostic significance of periodic acid-Schiff (PAS) stain in 112 serous: 43 benign, 25 borderline and 44 malignant cystadenomas: and in 106 mucinous: 60 benign, 32 borderline and 14 malignant cystadenomas of the ovary were investigated. The amount of positively stained mucin was estimated morphometrically. The outcome of most patients with benign or borderline lesion was good. One patient with benign mucinous cystadenoma died, however, of pseudomyxoma peritonei and another patient with borderline mucinous cystadenoma died of peritoneal carcinosis. Other patients were alive and free of the disease after a follow-up of 1-14 years, or had died of causes unrelated to the ovarian disease. Abundant PAS positive mucin predicted a longer survival both in serous and in mucinous malignant tumors. The 5-year survivals for the serous cystadenocarcinomas with and without PAS positive mucin were 21% and 13%, respectively (not statistically significant). For mucinous cystadenocarcinomas with mucin value over and below the median, the 5-year survival rates were 57% and 14%, respectively (P less than 0.10). High PAS positivity in both serous and mucinous cystadenocarcinomas clearly indicated better prognosis, although statistical significance was not achieved. Thus, further studies are needed for final evaluation of the prognostic significance of the PAS stain in these ovarian tumors.     

Diagnostic approach using the expression profiling of the P53 tumor suppressor gene and its related proteins in ovarian epithelial tumors

The initial aim of this study was to examine the expression profiles of P53 and its upstream genes, downstream genes, and cell cycle regulators to determine whether these markers are useful for making a differential diagnosis among the benign, borderline, and malignant ovarian epithelial tumors. Between borderline and malignant tumors, the increased expression levels of P53, Bax, Cyclin E, and cyclin-dependent kinase-2 as well as the decreased expression levels of growth arrest and DNA damage (GADD45) and murine double minute-2 (MDM2) were significantly associated with malignancy (P < 0.01, each). Using the receiver operating curve (ROC), the most reliable cutoff value of the added-up staining scores of those markers was 4.5 with 79% sensitivity and 89% specificity for malignancy. Between benign and borderline tumors, the P21 and Bax expression levels were significantly higher in borderline tumors, whereas the Bcl-2 expression level was much higher in benign tumors (P < 0.01, each). Using the ROC, the cutoff value of the added-up staining scores used to discriminate between the two groups was 2.5 with 70% sensitivity and 74% specificity for borderline tumors. Thus, for the differential diagnosis between borderline and malignant tumors, the cutoff value 4.5 of the cumulative staining scores can be used. However, the cutoff value 2.5 for discrimination between benign and borderline tumors may not be useful because of its relatively low sensitivity and specificity. In addition, the P53, GADD45, Cyclin E, and MDM2 expression levels in malignant ovarian tumors might be useful for determining the histologic grade and type.     

Placental leucine aminopeptidase (P-LAP) and glucose transporter 4 (GLUT4) expression in benign, borderline, and malignant ovarian epithelia

OBJECTIVE: Increased glucose consumption is a characteristic of malignant cells. Glucose is transported into the cell via facilitative glucose transporters, which are known to be members of a supergene family. The insulin-responsive GLUT4 isoform is expressed almost exclusively in insulin target tissues. P-LAP is a cell surface aminopeptidase, and is a synonym for oxytocinase. P-LAP is also referred to as insulin-regulated membrane aminopeptidase (IRAP) associated with GLUT4-containing vesicle. The authors evaluated P-LAP and GLUT4 expression in benign, borderline, and malignant ovarian epithelia. METHODS: Histologic sections of formalin-fixed, paraffin-embedded specimens from 11 patients with benign serous or mucinous cystadenomas, 14 patients with serous or mucinous borderline tumors, and 80 patients with epithelial-ovarian adenocarcinomas (29 serous, 17 endometrioid, 14 mucinous, and 20 clear cell adenocarcinomas) were stained for P-LAP and GLUT4 using each polyclonal antibody. Expressions of P-LAP and GLUT-4 in ovarian cancer cells were detected by Western blotting. RESULTS: P-LAP immunoreactivity was detected in 2 of 11 benign cystadenomas. None of the 11 benign ovarian tumors showed any immunoreactivity for GLUT4. Seven of 14 borderline tumors demonstrated P-LAP immunoreactivity, while 5 of 14 borderline tumors demonstrated GLUT4 immunoreactivity. P-LAP was expressed in 23 of 29 in serous, 15 of 17 endometrioid, 13 of 14 mucinous, and all clear-cell adenocarcinomas. The tendency toward increased P-LAP expression with advancing grade was observed in serous adenocarcinomas. GLUT4 was expressed in 13 of 29 serous, 13 of 17 endometrioid, 13 of 14 mucinous, and 18 of 20 clear-cell adenocarcinomas. In invasive carcinomas, there was a direct correlation between P-LAP immunoreactivity and GLUT4 immunoreactivity (correlation coefficient [r] = 0.58; P < 0.01). Furthermore, P-LAP overexpression in SKOV3 cells induced the GLUT4 expression. CONCLUSIONS: P-LAP and GLUT4 are available not only for the evaluation of ovarian epithelial malignancy, but also as targets for molecular therapy. Further study to investigate the roles of P-LAP and GLUT4 in ovarian carcinoma is needed.     

环氧合酶-2蛋白及前列腺素类物质与卵巢浆液性癌生物学行为的关系

目的　研究环氧合酶 2 (COX 2 )以及前列腺素类物质与卵巢浆液性肿瘤发生、发展的关系。方法　采用免疫印迹法及放射免疫法对 5 4例卵巢浆液性肿瘤组织 (其中良性卵巢浆液性肿瘤 11例 ,交界性良性卵巢浆液性肿瘤 10例 ,卵巢浆液性癌 3 3例 )和 10例正常卵巢组织进行COX 2蛋白、前列腺素 (PG)E2 、6 酮 前列腺素F1α(6 keto PGF1α)及血栓素 (TX)B2 水平检测。结果　 (1)COX 2蛋白表达 :卵巢浆液性癌组织的阳性表达率为 82 % (2 7/ 3 3 )、相对含量为 2 0 0 8± 3 5 3 ,交界性卵巢浆液性肿瘤分别为 90 % (9/ 10 )、2 0 61± 3 0 3 ,均明显高于良性卵巢浆液性肿瘤及正常卵巢 (阳性表达率均为0 ,相对含量分别为 15 0 4± 0 12及 15 3 3± 0 60 ) ,差异均有显著性 (P <0 0 5 ) ;卵巢浆液性癌患者不同临床分期 (Ⅰ～Ⅱ期与Ⅲ～Ⅳ期 )、病理分级及有无腹水、有无淋巴结转移间比较 ,差异均无显著性 (P>0 0 5 )。 (2 )前列腺素类物质PGE2 、6 keto PGF1α及TXB2 水平 :卵巢浆液性癌明显高于交界性、良性肿瘤和正常卵巢 (P <0 0 5 ) ,而后 3者间比较 ,差异无显著性 (P >0 0 5 ) ;卵巢浆液性癌患者不同临床分期 (Ⅰ～Ⅱ期与Ⅲ～Ⅳ期 )、病理分级及有无腹水、有无淋巴结转移间比较 ,差异均无显著性 (     

术前诊断卵巢交界性肿瘤的超声特征

目的探讨卵巢交界性肿瘤的术前超声特点，以便早期诊断。方法总结分析1995年10月-2005年12月，在我院住院手术的卵巢交界性肿瘤患者，术前经阴道超声检查、多普勒血流频谱检测，手术病理证实为交界性卵巢肿瘤的患者共54例，年龄18-82岁。同时与同期手术的卵巢良性上皮性肿瘤60例、I期卵巢癌22例做对比。结果54例卵巢交界性肿瘤中，浆液性19例，黏液性28例，混合型7例。其中浆液性肿瘤与黏液性肿瘤相比，肿瘤体积小（P=0．003）、单房多见（P〈0．001）、其内多有乳头与实性区（P〈0．001）。54例卵巢交界性肿瘤中，29／54（53．70％）例内壁有乳头或实性区，良性肿瘤7／60（11．67％）例内壁有乳头或实性区，I期卵巢癌20／22（90．91％）例内壁有乳头或实性区（P〈0．001）。50例交界性肿瘤行彩色多普勒检查，45／50（90．00％）例可探测到血流信号（与良性肿瘤相比P〈0．001；与I期卵巢癌相比P=0．297），其中29例阻力指数〈0．50。结论经阴道超声检查发现卵巢囊性肿物内出现乳头状突起、实性区或密集房隔、房隔增厚时应警惕有可能为交界性肿瘤，如联合多普勒血流频谱检测肿瘤阻力指数〈0．50更有助于术前诊断。     

卵巢浆液性和粘液性肿瘤共享结肠癌抗原决定簇

以抗结肠癌单克隆抗体ＳＣ１３Ａ为探针，应用免疫组织化学染色法，分别对６７例卵巢浆液性和４４例卵巢粘液性肿瘤组织，以及２０例正常卵巢组织中相应的抗原表达进行检测。结果：在浆液性囊腺瘤、交界性囊腺瘤和乳头状囊腺癌中ＳＣ１３Ａ抗原的表达率分别为８．０％，７１．４％和９０．０％；在粘液性囊腺瘤、交界性囊腺瘤和乳头状囊腺癌中ＳＣ１３Ａ抗原的表达率分别为２５．８％、８０．０％和８７．５％；正常卵巢组织中无３Ｃ１３Ａ抗原表达。浆液性、粘液性的交界性囊腺瘤和乳头状囊腺癌的抗原表达率，均显著高于浆液性、粘液性囊腺瘤及正常卵巢组织（Ｐ＜０．００５）。提示：浆液性和粘液性肿瘤抗原之间有内在的联系，这两类肿瘤的抗原中均共同享有与结肠癌抗原相同的抗原决定簇，这种抗原位点在恶性肿瘤中的表达明显高于良性肿瘤。     

Mucinous tumors of the ovary: analysis of 38 cases.

Ovarian mucinous tumors stem from ovarian surface epithelium and are divided into benign, borderline and malignant. It is difficult to differentiate borderline and malignant mucinous tumors. Thirty-eight cases of ovarian mucinous tumors which were diagnosed at the Pathology Department of Dicle University Medical Faculty were reviewed. Of these, 18 (47.3%), six (15.7%) and 14 (36.8%) were benign, borderline and malignant, respectively. The patients' ages ranged from 18 to 67 (average 44.5) years. Bilaterality was detected in 1/18 (5.5%), 0/6 and 4/14 (28.5%) of benign, borderline and malignant mucinous tumors, respectively. Mean tumor size was 26.4 cm. Microscopically, there was no stratification in the benign tumors. The borderline tumors had papillary infoldings and 2-3 layers of atypical epithelial cells but no invasion of the stroma. Malignant tumors had four or more layers of atypical epithelial cells and stromal invasion.     

Germ line and somatic mutations of BRAF V599E in ovarian carcinoma

It has been shown that ovarian low-grade serous carcinoma evolves out of a stepwise progression from benign serous cystadenoma to serous borderline tumor (SBT) to micropapillary serous carcinoma (MPSC), and that BRAF activation is a very early somatic event in the tumorigenesis. We postulated that BRAF could be a SBT susceptibility gene, and investigated both germ line and somatic mutations of BRAF V599E in 104 ovarian cancer patients. BRAF V599E mutation in histologic samples was found in 5 (24%) of 21 SBTs, 1 (33%) of 3 MPSCs, 1 (17%) of 6 endometrioid carcinomas, but not detected in 42 conventional serous carcinomas, 12 mucinous borderline tumors, 10 mucinous, and 10 clear-cell carcinomas. No V599E mutation could be detected in blood samples from these 104 patients. We also found no BRAF V599E mutation in 101 normal healthy women and 10 well-established ovarian cancer cell lines. Our results suggest that BRAF gene plays a "gatekeeper" role but does not act as a predisposition gene in the development of low-grade serous carcinomas.     

Accuracy of frozen section in the diagnosis of malignant ovarian tumor

AIM: To evaluate the diagnostic accuracy of frozen section for histopathologic diagnosis of ovarian tumors. METHODS: A total of 147 surgically removed ovarian tumors were studied. Each ovarian tumor sample was evaluated for histopathologic diagnosis using both frozen and paraffin sections. Interpretation was separate and blinded between each technique. Accuracy, diagnostic values and their 95% confidence intervals (CI) were estimated by comparing the results from both techniques, using paraffin section as a gold standard. RESULTS: Overall accuracy of frozen section was 89.8% (95% CI 83.4-94.0). Sensitivity was 90.4% (95% CI 78.2-96.4) for malignant, 33.3% (95% CI 6.0-75.9) for borderline, and 93.3% (95% CI 85.4-97.2) for benign tumors. The predictive value was 100% (95% CI 90.6-100) for malignant, 20% (95% CI 3.5-55.8) for borderline, and 92.2% (95% CI 84.1-96.5) for benign tumors. Most false negatives occurred in mucinous and borderline tumors. No benign tumor was misdiagnosed as malignant by frozen section. Accuracy and negative predictive value were significantly lower in epithelial rather than germ and other cell types. Excellent agreement with regard to histologic cell type was observed (Kappa 0.81). CONCLUSION: Frozen section appears to be an accurate technique for the histopathologic diagnosis of ovarian tumors. Some limitations were observed among borderline and mucinous tumors; this emphasizes the great value of frozen section in the diagnosis of ovarian tumors.     

Cyclooxygenase 2 expression in serous tumors of the ovary.

This study was designed to investigate the expression of cyclooxygenase (COX)-2 in ovarian serous tumors (benign, borderline tumors, and carcinomas) and primary peritoneal serous carcinomas. Cases diagnosed between 1995 and 2001 were reviewed; 47 benign tumors, 6 borderline tumors, and 39 carcinomas were examined, as well as 12 normal ovaries that served as controls. Blocks were stained with anti COX-2 polyclonal antibody and staining was graded qualitatively. The staining intensity was assessed as weak (score of 1), moderate (score of 2), or strong (score of 3). Normal ovarian and tubal epithelium, inclusion cysts, benign serous tumors, and borderline tumors had a uniform score 3 staining pattern. Serous ovarian carcinomas had variable staining scores, tending to correlate with the level of tumor differentiation. Well-differentiated carcinomas had more intense COX-2 staining than poorly differentiated carcinomas, which had only weak COX-2 staining. The degree of COX-2 staining was not significantly related to overall survival. In conclusion, COX-2 expression is present in serous tumors, including benign tumors, borderline tumors, and carcinomas. Similar to the findings in other neoplasms, COX-2 expression is strongest in well-differentiated tumors and is much less evident in those that are poorly differentiated. The clinical utility of these findings is related to the potential role of nonsteroidal anti-inflammatory drugs, which are COX-2 inhibitors, in treating and/or preventing some forms of ovarian carcinoma.     

Neutral endopeptidase/CD10 expression in the stroma of epithelial ovarian carcinoma.

This study investigated the immunohistochemical expression and localization of neutral endopeptidase (NEP) (CD10), which plays a functional role by degrading bioactive peptides, in ovarian tumors. In normal ovaries and benign cystadenomas, NEP was not detected in any epithelial or stromal cells. In borderline tumors, NEP was detected in the stromal cells in 6 of 7 serous tumors, but not in those from mucinous tumors. In ovarian carcinomas, NEP in the stromal cells was observed in 13 of 20 serous, 8 of 10 endometrioid, and 7 of 10 clear-cell adenocarcinomas. NEP was weakly detected in only 1 of 9 mucinous adenocarcinomas. The staining intensity of stromal NEP was decreased in grades 2 and 3 serous carcinomas compared with that in grade 1 serous carcinomas. In conclusion, NEP was specifically expressed in the stroma of borderline and malignant ovarian tumors, but not in adenomas. Furthermore, stromal NEP was downregulated as the histological grade advanced. These results suggest that NEP may play a role in the regulation of neoplastic transformation and tumor differentiation in epithelial ovarian carcinomas.     

卵巢上皮性肿瘤中黏蛋白MUC2和MUC5AC的表达及意义

目的 研究卵巢上皮性肿瘤中黏蛋白MUC2和MUCSAC的表达，探讨它们在卵巢上皮性肿瘤恶性进展中的作用及其临床意义。方法 采用免疫组化方法SP法检测20例良性、23例交界性和37例恶性卵巢上皮性肿瘤中黏蛋白MUC2和MUCSAC的表达。结果 黏蛋白MUC2和MUCSAC表达水平随卵巢黏液性肿瘤恶性程度的增加而表达增高。黏蛋白MUC2的表达与肿瘤的病理分级和临床分期密切相关，而黏蛋白MUCSAC与病理分级和临床分期无关。结论 卵巢黏液性肿瘤发生早期肿瘤细胞即有胃型和肠型的分化，并且随着肿瘤的恶性进展持续存在。检测黏蛋白MUC2的表达可作为预测卵巢癌预后的有价值的指标。。     

Histologic sampling requirements in ovarian carcinoma: a review of 51 tumors

In a review of 29 serous and 22 mucinous adenocarcinomas of the ovary, we quantitated the various histologic patterns seen in these neoplasms in order to document histologic variability and assess current anecdotal recommendations (one section per 1-2 cm of maximum tumor diameter) for adequate histologic sampling of epithelial ovarian neoplasms. Mucinous carcinomas showed more histologic variation than serous carcinomas, but both showed substantial portions with benign or borderline histology in many neoplasms. One serous and one mucinous carcinoma were likely to have been classified as borderline tumors if only current sampling recommendations had been followed. The remaining adenocarcinomas were adequately sampled by current standard practice. The two tumors in question had unusual clinical and histological features which prompted additional sampling. Caution is particularly warranted when initial frozen section sampling shows features of borderline tumor histology or low grade epithelial atypia, especially in mucinous epithelial neoplasms where histologic variability is greatest.     

k-ras mutation may be an early event in mucinous ovarian tumorigenesis.

We explored the possible pathogenetic pathway for mucinous ovarian tumorigenesis by examining the k-ras mutational patterns in ovarian mucinous tumors (OMTs) with benign, borderline, and invasive epithelium in which the different types of mucinous epithelium are in close proximity. Sixteen patients with ovarian mucinous borderline tumors (OMBTs) and 4 patients with grade 1 ovarian mucinous adenocarcinomas (OMCs) were selected for the presence of a single histologic section which contained a clear "transition" zone from benign mucinous epithelium to borderline mucinous epithelium, and in four cases, to invasive epithelium. A PixCell II Laser Capture Microscope was used to microdissect and retrieve benign, borderline, and invasive epithelium separately from the 20 OMTs. Normal ovarian stroma from the same histologic section in each case was also microdissected and retrieved for use as a control. k-ras mutations were detected in these samples by PCR-SSCP analysis followed by direct PCR cycle sequencing. k-ras mutations were found in 8/16 (50%) of the OMBTs and 2/4 (50%) of the grade 1 OMCs. In 6 of these 10 cases (4 in OMBTs, 2 in grade 1 OMCs), the same k-ras mutation was found in both the benign and borderline (and invasive) regions. In 3 cases in which k-ras mutations were identified, the mutation was found in either the benign or borderline tissue samples alone, and in one case, two distinct mutations were found. No k-ras mutations were identified in the normal ovarian stroma. The presence of a k-ras mutation in adjacent benign and borderline regions of a single OMT may suggest a progression in the development of OMTs from benign to borderline and grade 1 OMCs. k-ras mutations, when they occur, are likely early genetic changes but may not alone be sufficient for malignant transformation of ovarian epithelium.     

An immunohistochemical study of the incidence and significance of C-erbB-2 oncoprotein overexpression in ovarian neoplasia

Abstract. Wilkinson N, Todd N, Buckley CH, Gusterson BA, Fox H. An immunohistochemical study of the incidence and significance of C-erb-B oncoprotein overexpression in ovarian neoplasia. Int J Gynecol Cancer 1991; 1 : 285–289.
An immunohistochemical study was made of overexpression of the c-erbB-2 oncogene product in benign, borderline and malignant epithelial neoplasms of the ovary. Positive staining was found only in 2 of 15 mucinous tumors of borderline malignancy and in 11 of 16 mucinous adenocarcinomas. Positive staining was not detected in serous or endometrioid tumors. Amongst the group of mucinous adenocarcinomas, no correlation could be found between overexpression of c-erbB-2 oncoprotein and tumor stage, tumor differentiation or patient survival. It is concluded that overexpression of c-erbB-2 oncoprotein is not an adverse prognostic factor in ovarian adenocarcinoma.     

卵巢浆液性癌B7-H4的表达及临床病理意义

目的:探讨B7-H4在卵巢上皮性肿瘤浆液性癌中的表达及其临床病理意义。方法:用逆转录聚合酶链反应(RT-PCR)技术及免疫组织化学染色的方法检测6例良性卵巢上皮性肿瘤、10例交界性卵巢上皮性肿瘤、41例卵巢浆液性癌、5例内膜样癌、2例透明细胞癌和10例粘液性癌标本中B7-H4 mRNA及蛋白表达,并结合临床病理资料对其中41例卵巢浆液性癌中B7-H4蛋白的表达进行分析。结果:B7-H4 mRNA在74例卵巢上皮性肿瘤中均有表达,B7-H4蛋白在良性卵巢上皮性肿瘤、交界性卵巢上皮性肿瘤、恶性卵巢上皮性肿瘤中的表达阳性比例分别为2/6、6/10、52/58,恶性标本阳性率明显高于非恶性标本,差异有统计学意义(P<0.05);58例恶性卵巢上皮性癌标本中浆液性癌、内膜样癌、透明细胞癌、黏液性癌的B7-H4蛋白阳性比例分别为41/41、5/5、2/2、4/10,前三种病理类型B7-H4蛋白阳性率明显高于最后一种,且差异有统计学意义(P<0.05);41例卵巢浆液性癌标本中B7-H4蛋白阳性细胞比例在<10%,>10%~50%,>50~80%,>80~100%4组中的分布差异无显著性(P>0.05),且其蛋白表达与临床分期及病理分级有关(P<0.05),而与患者年龄、腹水细胞学、淋巴结转移无关(P>0.05)。结论:B7-H4在卵巢浆液性癌的高表达及其与临床分级分期的关系,提示其可能与肿瘤发生发展有关,可为卵巢恶性肿瘤诊断及治疗提供靶位点。