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.     

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。     

Study of borderline and invasive mucinous ovarian tumors using Ki-67 (MIB 1) antibodies and nucleolar organizer region (NOR) staining

Extensive application of new methods in histopathology has resulted in large quantities of data on molecular markers in different types of human tumors. The main purpose has been to obtain additional parameters for the characterization of various types of malignancy to give more precise information on their biological behavior. In this study we tested AgNOR and Ki-67 (MIB1) staining in 39 ovarian mucinous tumors to evaluate its diagnostic potential in distinguishing between borderline tumors and well-differentiated carcinomas at stage I of FIGO classification. In general, there was an increase in AgNOR median values from benign (1.83 ± 0.8) to well-differentiated carcinomas (2.91 ± 1.3) with an intermediate value in borderline (2.3± 1.6). The lowest Ki-67 labeling index (LI) was found in benign cystadenomas (5.7% ± 3.4%) and papillary mucinous cystadenomas (7.9 ± 5.8%). In borderline tumors mean LI was 12.2 ± 10.9% whereas well-differentiated carcinomas had higher LI (16.8 ± 10.2%). There were no statistically significant differences between the evaluated tumors and techniques applied. In our opinion the AgNOR count and Ki-67 LI do not appear useful for assessing differences between borderline and well-differentiated mucinous ovarian tumors at stage I of clinical advancement. Received: 15 October 1998 / Accepted: 4 March 1999     

Appendiceal tumors in patients undergoing primary surgery for mucinous ovarian tumors in a tertiary hospital,in Southern Thailand

ObjectiveTo evaluate the prevalence of appendiceal tumors in patients diagnosed with mucinous ovarian tumors and to determine factors associated with coexisting appendiceal tumors.Materials and methodsRetrospective review of all patients who were diagnosed with mucinous ovarian tumors and underwent an appendectomy during surgery between January 2002 and June 2017 was performed. Univariate and multivariate logistic regression analyses were used to identify risk factors for coexisting appendiceal tumors.ResultsA total of 303 patients with mucinous ovarian tumors who underwent appendectomy were identified, including 77 (25.4%) mucinous cystadenoma and 226 (74.6%) mucinous borderline tumor or carcinoma. Twenty-one (6.9%) had coexisting appendiceal tumors including 8 that were primary appendiceal mucinous adenocarcinomas, 6 low-grade appendiceal mucinous neoplasms, 6 secondary appendiceal metastasis from the ovary, and one hyperplastic polyp. None of mucinous cystadenoma had coexisting appendiceal tumors. Multivariate analysis revealed advanced age ≥50 years, previous rupture of ovarian tumors, abdominal extension of tumors, and grossly abnormal appendix were independent factors for coexisting appendiceal tumors.ConclusionPrevalence of coexisting appendiceal tumors in mucinous ovarian tumors was not uncommon. The risk factors were grossly abnormal appendix, abdominal extension of tumor, previous rupture of ovarian tumors, and advanced age.     

Immunolocalization of alpha-amylase in ovarian mucinous tumours

The distribution of alpha-amylase was studied immunohistochemically in 42 cases of ovarian mucinous tumour. Intense immunoreactivity for amylase was found in 6 of 8 cases of mucinous cystadenocarcinoma. In contrast, only 6 of 20 benign mucinous cystadenomas showed immunoreactive amylase, which was weak and patchy. Mucinous cystadenomas of borderline malignancy showed an intermediate degree of amylase immunoreactivity. The patterns seen are very similar to those reported in normal endocervix, cervical glandular atypia, and invasive adenocarcinoma and suggest molecular as well as morphologic similarities in neoplasia at these sites.     

Prognostic importance of the nucleolar organizer region score in ovarian epithelial tumors

OBJECTIVE: The score of the silver-stained nucleolar organizer region (AgNOR) is frequently found to be high in malignant tumors. We studied AgNOR in ovarian epithelial tumors diagnosed in our hospital between 1993 and 1998. MATERIALS AND METHOD: In our study 67 ovarian epithelial tumors (18 cystadenoma, 16 borderline type, 34 cystadenocarcinoma) were stained using the method previously described by Crocker. One-way ANOVA and logistic regression tests were used to find the statistical relationship between grade, recurrence, mortality rates and AgNOR scores in tumors (p values of <0.05 were considered statistically significant). RESULTS: The mean AgNOR scores of 28 mucinous and 39 serous ovary tumors were calculated. The lowest AgNOR score of 1.33 was found in cystadenomas and the highest AgNOR score of 4.92 was found in serous and mucinous cystadenocarcinomas. In addition the relationship between mortality rate, recurrence and AgNOR score in carcinomas were studied. CONCLUSION: AgNOR scores in carcinomas were found to be higher than adenomas, and the highest AgNOR score was found in grade-III carcinomas. This shows that the AgNOR score can be used as a prognostic index in malignancies.     

The Blood Flow Characteristics in Borderline Ovarian Tumors Based on Both Color Doppler Ultrasound and Histopathological Analyses

To clarify the tumor behavior in borderline ovarian tumors, we examined the characteristics of neovascularization in these tumors by using a transvaginal color Doppler ultrasound (TV-CDU). Twelve patients with borderline ovarian tumors were preoperatively evaluated for the characteristics of intratumoral blood flow by TV-CDU, using both the resistance index (RI) and pulsatility index (PI). As a control group, 100 patients with benign ovarian tumors and 31 patients with malignant ovarian tumors were also examined by TV-CDU. An intratumoral blood flow was significantly detected in both borderline (91.6%; 11/12) and malignant ovarian tumors (90.3%; 28/31), but not in benign ovarian tumors (53%; 53/100) (P< 0.01). In addition, both the mean RI and mean PI values were significantly lower in the borderline (RI; 0.45, PI; 0.67) and malignant ovarian tumors (RI; 0.39, PI; 0.58) than those in the benign ovarian tumors (RI; 0.61, PI; 1.05) (P< 0.01). In mucinous tumors, the borderline tumors showed a significantly high intratumoral vascularity (P< 0.01) and both borderline and malignant tumors significantly demonstrated a low-resistance blood flow (P< 0.01), in comparison to those of the benign tumors. Mucinous borderline tumors of the intestinal type also tended to have a lower RI as well as a lower PI value than müllerian type. Regarding neovascularization as represented by intratumoral blood flow characteristics, this study thus suggests that a close relationship exists in the tumor behavior between borderline and malignant ovarian tumors, especially in mucinous epithelial tumors.     

CA 125 measurement and ultrasonography in borderline tumors of the ovary

OBJECTIVES: Our goal was to perform an analysis of ultrasonographic characteristics and CA 125 levels in ovarian tumors of borderline malignancy. STUDY DESIGN: We performed a retrospective analysis of CA 125 levels and ultrasonographic parameters in 91 patients with borderline tumors. RESULTS: Serous tumors of borderline malignancy were associated with elevated CA 125 levels in 75% of patients before surgery (mean, 156 IU/mL) compared with 30% of mucinous tumors (mean, 28 IU/mL; P =.004). CA 125 was elevated in 35% of stage IA serous tumors (mean, 67 IU/mL) compared with 89% of tumors with spread beyond the ovary (mean, 259 IU/mL; P =.001). Mucinous tumors tended to be bigger (13.1 +/- 7 cm) on ultrasonography than serous tumors (9.3 +/- 6.2 cm, P =.016). Mucinous tumors were multilocular in half the patients and contained papillations in 40% of the patients. Serous tumors were multilocular in 30% of the patients but presented with solid or papillary patterns in 78% of the patients (P =.001). A resistance index of <0.4 was found in 36% of mucinous tumors and half the cases of serous tumors. In 13% of patients, ultrasonographic characteristics were compatible with a simple cyst only, including 1 patient with microinvasion and 1 patient with stage IIIB disease. Sensitivity of gray-scale ultrasonography was 87%, that of CA 125 measurement was 62%, and that of flow was 55%. At least 1 diagnostic test result was abnormal in 93% of patients, 2 were abnormal in 69% of patients, and all 3 were abnormal in 21% of patients. CONCLUSIONS: A high proportion of borderline tumors of the ovary, particularly of the serous type, were associated with elevated CA 125 levels and abnormal ultrasonographic characteristics, although some tumors presented as simple cysts.     

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。     

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.     

Demonstration of neuroendocrine cells in ovarian mucinous tumors

The frequency of argyrophil cells in mucinous cystadenocarcinomas, borderline tumors (MBT) and cystadenomas was 29.8% (14 of 47), 46.7% (7 of 15) and 11.1% (2 of 18), respectively. These were statistically higher than the frequencies in 17 clear cell carcinomas, 43 serous cystadenocarcinomas, and 24 metastatic carcinomas. Immunoreactive cells for serotonin, somatostatin, gastrin, pancreatic polypeptide, growth hormone-releasing hormone, metenkephalin, neuron-specific enolase, and chromogranin-A were detected in almost all these cases with argyrophil cells. However, immunoreactivities for glucagon, vasoactive intestinal polypeptide, and adrenocorticotropic hormone were negative in ovarian mucinous tumors. Immunohistochemical multiplicity of neurohormones was remarkable in 15 MBT (including 5 müllerian and 10 intestinal MBT) and it was not related to the number of argyrophil cells per unit tumor cells. Individual hormones demonstrated here seemed to be present in different cells, but certain cells were immunoreactive for both gastrin and somatostatin by double immunostaining. Based on the high frequency of endocrine cells, borderline tumors seemed to be unique in the spectrum of mucinous ovarian tumors.     

Expression of epidermal growth factor receptors in benign ovarian tumors

The objective of the present study was to determine the level of EGFR expression in patients having benign ovarian tumors and in morphologically normal ovarian tissue by quantitative ligand binding assays. In a prospective study 42 patients with benign ovarian tumors and 30 with normal ovaries were included. In the group of patients expressing EGFR, those having benign tumors were 23 (64%) and the ones with normal ovaries--13 (36%). The average level of EGFR expression was the highest in the cases of teratoma adultum (110 fmol/mg), followed by mucinous (97 fmol/mg) and serous (30 fmol/mg) cystadenomas. The differences between the average levels of EGFR expression in mucinous and serous benign ovarian tumors were significant (p = 0.032), as for the remaining histological variants--statistically insignificant (p = 0.086). Mucinous cystadenomas possessed higher proliferative potential compared to serous cystadenomas.     

Transition from benign to malignant epithelium in mucinous and serous ovarian cystadenocarcinoma.

The slides of all patients with ovarian cystadenocarcinoma treated at the University of Kentucky Medical Center from 1966-1990 were reviewed. Fifty-four serous tumors and 42 mucinous neoplasms were identified for further study. Benign epithelium adjacent to an area of borderline or malignant epithelium was observed in 74 tumors (79%) and a site of epithelial transition was noted in 38 cases (40%). The presence of associated benign epithelium was more common in borderline or well-differentiated lesions and in patients with early-stage disease. These findings are consistent with epidemiologic and molecular genetic data and suggest that certain benign serous or mucinous ovarian tumors have the potential for malignant transformation. Removal of these tumors, particularly in postmenopausal women, should result in a subsequent reduction in the frequency of ovarian cancer.     

Prevention of Recurrent Mucinous Borderline Ovarian Tumor with Aromatase Inhibitor

BackgroundAromatase inhibitors (AIs) are used for estrogen-modulated conditions. Some borderline ovarian tumors (BOT) express estrogen receptors. We present 2 cases of progression from mucinous cystadenoma to mucinous BOT (mBOT) after prior cystectomies in whom an AI was used with recurrence prevention.CasesTwo patients underwent laparoscopic ovarian cystectomy for mucinous cystadenoma. Serial imaging demonstrated recurrent ovarian cysts for which both underwent fertility sparing surgery (FSS) with ovarian cystectomy for mBOT. Both patients were initiated on an AI and have been without recurrence.Summary and ConclusionBOT predominantly occur in reproductive aged females. FSS with cystectomy is an option, but recurrence occurs in 12-36% of cases. The use of AI in prevention of recurrent BOT shows promise, and more studies are needed to explore this treatment.     

Mucosubstances in classification of serous and mucinous ovarian tumors: a morphometrical study

108 serous and 106 mucinous ovarian cystadenomas of varying malignancy were studied with the saliva-periodic acid-Schiff (SPAS) reaction and with the Alcian blue (AB) pH 2.7 method, which stain neutral and acid mucosubstances, respectively. Positively stained mucin was quantitated morphometrically and the measured parameters were tested by discriminant analysis. As expected, the mucinous tumors were more positive for mucin than the serous ones. Also the borderline tumors contained more mucin than their benign or malignant counterparts. The best discriminating capacity for mucin was obtained in serous tumors with the AB stain and in mucinous tumors with the SPAS reaction. The ratio of neutral to acid mucosubstances decreased in mucinous cystadenomas with increasing malignancy.     

CA_(125)、CA_(19.9)、CEA在卵巢上皮性交界性肿瘤中的临床价值

目的 :探讨测定血清CA12 5、CA19.9、CEA在诊断卵巢上皮性交界性肿瘤中的临床价值。方法 :回顾分析卵巢交界性肿瘤 5 0例血清CA12 5、CA19.9、CEA水平与临床资料。结果 :浆液性及粘液性肿瘤中CA12 5的阳性率分别为 5 3.85 %和 60 % ,差异无显著性 (P >0 .0 5 ) ,临床分期晚者CA12 5阳性率有增高趋势 ;粘液性肿瘤中CA19.9的阳性率为 4 3.75 % ;CEA阳性率为 12 % ,仅见于粘液性或以粘液性为主的肿瘤中 ;与术前相比 ,术后CA12 5、CA19.9水平及阳性率均显著下降 (P <0 .0 5 )。结论 :CA12 5、CA19.9对卵巢上皮性交界性肿瘤的术前诊断及疗效监测有一定价值 ,CEA则在鉴别组织学类型中有一定价值。     

Laparoscopic management of a large recurrent benign mucinous cystadenoma of the ovary

Introduction Benign mucinous cystadenomas account for 15% of all ovarian neoplasms and up to 80% of all mucinous tumors. Laparoscopy has become an accepted method of management for ovarian cysts and its role is expanding as large benign adnexal masses more than 10 cm can be managed safely and effectively. Case report We report a 25-year-old nulliparous lady with a huge benign mucinous cystadenoma managed by laparoscopic cystectomy, followed by an early recurrence within 2 months. Left salpingo-oophorectomy was performed on a repeat laparoscopy due to suspicion of malignancy on ultrasound. Pathology revealed a benign cyst. Conclusion Since mucinous tumors are usually benign and multilocular, management of young patients is challenging, especially in the case of recurrence which is very rare.     

Hypoxic status in ovarian serous and mucinous tumors: relationship between histological characteristics and HIF-1α/GLUT-1 expression

Material and methods We analyzed the expression of hypoxia inducible factor-1α (HIF-1α) and glucose transporter-1 (GLUT-1) by immunohistochemistry in ovarian serous and mucinous tumors from the point view of the histological characteristics and acquisition of malignancy. A total of 102 ovarian tumors were examined, composed of 31 adenomas (serous 17 and mucinous 14), 32 borderline tumors (serous 13 and mucinous 19), and 39 adenocarcinomas (serous 21 and mucinous 18). Results The overall positive ratios were as follows: HIF-1α, 74% of adenomas, 91% of borderline tumors, and 100% of adenocarcinomas; and GLUT-1, 68% of adenomas, 95% of borderline tumors, and 100% of adenocarcinomas. Comparing serous tumors and mucinous tumors, there was no significant difference in the positive ratios of HIF-1α and GLUT-1 of adenomas, borderline tumors, and adenocarcinomas. However, both markers were more strongly expressed in serous adenocarcinomas (HIF-1α, 3 + 100%; GLUT-1, 3 + 76%) than in mucinous adenocarcinomas (HIF-1α, 3 + 61%; GLUT-1, 3 + 28%). The results of immunoblotting and mRNA expression level analyses corresponded with those of immunohistochemical expression profiles. DNA binding assay also demonstrated that HIF-1 is more commonly activated in serous adenocarcinomas than in mucinous adenocarcinomas. Conclusion HIF-1α and GLUT-1 expressions seemed to be coordinated to adapt ovarian tumor cells into hypoxic conditions in close association with the acquisition of malignancy. We consider that the relatively strong expression of both markers in serous tumors compared with mucinous tumors is related to the difference in their histological characteristics.     

Preoperative serum CA-125 levels in borderline tumors of the ovary.

Preoperative serum CA-125 levels were evaluated in 38 patients who underwent primary surgery for epithelial ovarian tumors of borderline malignancy at the Brigham and Women's Hospital and Massachusetts General Hospital between 1981 and 1990. Surgical staging was Stage I in 25 (66%) patients, Stage II in 2 (5%) patients, Stage III in 10 (26%) patients, and Stage IV in 1 (3%) patient. The mean sizes of mucinous and serous ovarian tumors were 21.9 and 10.3 cm, respectively (P = 0.0002). All 13 patients (100%) with mucinous tumors had Stage I disease, while 12 (50%) of 24 patients with serous tumors were Stage I. Combining all cell types, 10 (40%) of 25 patients with Stage I disease had an elevated preoperative CA-125 level, while 2 (100%) of 2, 9 (90%) of 10, and 1 (100%) of 1 patient with Stage II, III, and IV disease, respectively, had increased preoperative levels. Among patients with serous tumors, 3 (25%) of 12 Stage I patients had an elevated preoperative CA-125 level, while 11 (92%) of 12 Stage II-IV tumors had elevated levels (P less than 0.001). These data suggest that preoperative CA-125 level correlates with stage of disease in patients with serous borderline ovarian tumors.     

Mucinous tumors of the ovary: a review.

Mucinous ovarian tumors are among the most difficult ovarian neoplasms for surgical pathologists to interpret. Approximately 20% of primary ovarian mucinous tumors are borderline tumors, noninvasive (intraglandular; intraepithelial) carcinomas, or invasive carcinomas; the remainder are cystadenomas. The borderline tumors may be of intestinal type or mullerian (endocervical-like) type. The intestinal-type tumors are by far the most common. Their frequently heterogeneous composition with coexisting elements of cystadenoma, stromal microinvasion, noninvasive carcinoma, and invasive carcinoma requires careful gross examination and extensive sampling of the tumors. The inherent glandular complexity of proliferating mucinous tumors complicates recognition of stromal invasion. Some mucinous carcinomas with expansile (confluent) invasion may be very difficult to discriminate from extensive noninvasive carcinoma. Interobserver reproducibility probably requires use of an arbitrary minimum size criterion for the diagnosis of expansile invasion. Primary invasive carcinomas with an infiltrative growth pattern are less common. Rarely, distinct mural nodules of reactive or neoplastic type are found in the cystic wall of a mucinous tumor. Pseudomyxoma peritonei almost never results from a ruptured primary ovarian mucinous neoplasm, but often produces secondary borderline-like ovarian tumors with prominent pseudomyxoma ovarii. Prognosis of mucinous tumors is highly dependent on stage and histologic composition. Borderline tumors, noninvasive carcinomas, microinvasive tumors, and invasive carcinomas with an expansile growth pattern are generally stage I and have an excellent prognosis with only occasional examples of metastatic spread. Invasive carcinomas with an infiltrative growth pattern are more aggressive, accounting for almost all high-stage mucinous tumors, and are responsible for most deaths caused by tumor. A high index of suspicion that a mucinous tumor is actually a metastasis from another organ is required by pathologists and gynecologists to prevent misdiagnosis of a metastatic neoplasm as a primary ovarian tumor. Secondary mucinous tumors are significantly more often bilateral, <10 cm in maximal dimension, and of high stage. Numerous immunohistochemical stains proposed to aid in the differential diagnosis of primary vs. secondary mucinous tumors also are reviewed.