Aggressive behavior of stage I ovarian mucinous tumors lacking extensive infiltrative invasion: a report of four cases and review of the literature.

Previous studies have indicated that mucinous carcinomas of the ovary associated with extraovarian spread at the time of presentation or follow-up almost always have extensive infiltrative invasion within the primary tumor. We present four cases of stage I ovarian mucinous tumors that lacked extensive infiltrative invasion but were associated with an unexpectedly aggressive behavior. The patients were 18, 20, 41, and 45 years of age at presentation. All four of them presented with an abdominal mass or increased abdominal girth. The tumors were all stage Ia, 17 to 37 centimeters in maximal dimension, and typically multicystic with solid areas. The number of blocks per centimeter of tumor diameter was 0.65, 0.88, 0.92, and 1.0 in the four tumors, respectively, a degree of sampling within that recommended in previous studies. Clinical findings supported that they were primary tumors rather than metastatic from an occult primary tumor. On microscopic examination, the tumors all contained foci of intraepithelial carcinoma and foci of invasion as follows: expansile invasion only (two cases), expansile invasion and microinvasive carcinoma (one case), and microinvasive carcinoma only (one case). The expansile invasion was extensive in each of the three cases in which it was present. On follow-up, each patient experienced recurrent disease 7 months to 4.5 years after diagnosis, including hematogenous spread to lung and/or bone and liver in three patients. Three of four patients developed intraperitoneal spread. Three of four patients died of disease, and one patient is alive with persistent disease. Although ovarian mucinous tumors with only expansile invasion or only microinvasive carcinoma are usually associated with an excellent prognosis, this study indicates that these tumors can rarely behave in an aggressive fashion with hematogenous spread and a fatal outcome. Some of these tumors may have contained unsampled foci of infiltrative invasion. Although the optimum level of sampling in mucinous tumors remains to be determined, we recommend additional sampling of tumors in which the initial sections reveal intraepithelial carcinoma, microinvasive carcinoma, expansile invasion, or combinations thereof.     

Ovarian mucinous and mixed epithelial carcinomas of mullerian (endocervical-like) type: a clinicopathologic analysis of four cases of an uncommon variant associated with endometriosis.

The epithelial cells of ovarian mucinous carcinomas may sometimes appear similar to those of gastrointestinal or endocervical mucinous carcinomas, but most are composed of cells that do not suggest any particular derivation. We report four cases of mucinous ovarian carcinoma in which the cells were entirely or almost entirely endocervical-like. The patients' ages were 34, 43, 44, and 50 years. Two patients had bilateral tumors confined to the ovaries at initial staging; both also had synchronous endometrial carcinomas of the mucinous type. The two other patients had unilateral tumors, both with invasive metastases in the pelvis and abdomen at initial staging. In one of the latter cases a mullerian (endocervical-like) mucinous borderline tumor (MMBT) of the opposite ovary had been removed 5 years earlier, and in this case and two other cases the ovarian carcinomas had foci resembling MMBT, suggesting that they may be an invasive counterpart to these tumors. The six tumors ranged from 4 to 19 cm; five were grossly cystic with papillary or solid areas, and one was entirely solid. They were composed of closely packed glands, cysts, and cysts containing complex papillae. There was abundant intraglandular and intracystic mucin. The epithelial cells were well differentiated with infrequent mitoses and most were tall with mucinous cytoplasm resembling normal endocervical glandular cells. In three tumors there also were round to polygonal cells with eosinophilic cytoplasm; endometrioid foci were present in three tumors and a squamous focus was present in one. One tumor had a focally infiltrative growth pattern with a desmoplastic stromal reaction; the remaining five tumors had an exclusively confluent (expansile) pattern of invasion. Endometriosis was present in residual ovarian tissue adjacent to four tumors in three patients and had marked epithelial proliferation in three. All patients were treated postoperatively with chemotherapy and were without clinical recurrence with follow-up intervals of 8 months, 1.2 years, 2.9 years, and 3.8 years. By immunohistochemical analysis the neoplastic epithelium was positive for estrogen and progesterone receptor proteins, vimentin, and cytokeratin 7, and negative or only focally positive for carcinoembryonic antigen and cytokeratin 20, a profile that differs from that of the usual mucinous ovarian carcinoma and is supportive of a mullerian derivation. As with MMBTs, there was a strong association with endometriosis, and these tumors likely arise from endometriosis, possibly through an MMBT precursor in some cases. To better understand their clinicopathologic features and pathogenesis, this uncommon variant should be separated from the usual type in future studies of mucinous carcinomas of the ovary.     

Borderline-Tumoren des Ovars

Borderline tumors of the ovary are intermediate between benign epithelial tumors (cystadenomas, adenofibromas) and invasive carcinomas, both morphologically and clinically. They contain atypical epithelial proliferations without destructive stromal invasion. Most borderline tumors are of the serous or mucinous types. There seems to be an increasing incidence of borderline tumors, the peak incidence being ten years earlier as compared to invasive carcinomas. There are no specific symptoms. A definitive diagnosis can only be made after meticulous histopathologic examination. Only surgical staging can reliably reveal the extent of tumor spread. Prognosis is very good in a vast majority of cases (ten year survival rate ≥90%). The most important prognostic factors are stage, invasive implants, residual tumor, histological type, and age of the patient. The significance of DNA ploidy is still a matter of controversy. If the conservation of fertility is not desired, surgical treatment of borderline tumors consists of bilateral adnexectomy (with optional hysterectomy), omentectomy, peritoneal biopsies, peritoneal washing, and appendectomy (in cases of mucinous borderline tumor). A less radical approach is possible for patients who wish to preserve fertility. No adjuvant chemotherapy is indicated in borderline tumors of the FIGO stage I/II and III (no invasive implants). Surgical resection is the preferred treatment for recurrent disease. Patients with borderline tumors should be followed up as recommended for ovarian cancer.     

Pathologic findings in eight cases of ovarian serous borderline tumors, three with foci of serous carcinoma, that preceded death or morbidity from invasive carcinoma.

We sought to assess the frequency of previously reported adverse histopathologic findings in ovarian serous borderline tumors (SBTs) in cases that preceded a patient's death or caused serious morbidity due to invasive carcinoma. SBTs with foci of invasive carcinoma that occupied a minority of the tumor and were associated with similar outcomes were also studied for potential additional insights. Eight cases were found over a 22-year period. Ten tumors in 5 patients were purely SBT; at initial staging, 1 patient had invasive peritoneal implants; 3 had noninvasive peritoneal implants; 1 was stage I. At last follow-up 3 of the 5 patients had died of carcinoma, 1 was alive with carcinoma, and 1 had no clinical evidence of disease 4 years after a sigmoid colectomy for invasive serous carcinoma of the bowel wall. Four tumors in 3 patients had foci of invasion that were more than microinvasive; at initial staging, all 3 patients had invasive peritoneal implants, and all died of carcinoma. All 14 of the ovarian tumors in the 8 cases had surface involvement by tumor cells, and in 8 tumors in 5 cases they were confined primarily to the ovarian surface. Foci of "micropapillary serous carcinoma" accompanied more obvious areas of infiltrative carcinoma in 2 of the 4 ovarian tumors, the peritoneal implants in 1 of the cases with purely SBTs, and a recurrence in this case and 1 other case. No morphologic finding in the 10 purely SBTs was predictive of subsequent malignant behavior. We conclude that extraovarian invasive serous carcinomas, either following or concurrent with an ovarian SBT, develop from borderline foci that may originate in the ovary, but frequently are likely to have arisen independently in the peritoneum. The carcinomas may be preceded or accompanied by noninvasive-appearing micropapillary foci in the peritoneum in some cases, but micropapillary foci in the ovarian tumors are infrequent and not a necessary antecedent.     

Differential expression of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 protein and mRNA in epithelial ovarian tumors

OBJECTIVE: Matrix metalloproteinase-9 (MMP-9) can degrade gelatin and type IV collagen and is known to play an important role in tumor cell invasion across the basement membrane. The tissue inhibitor of metalloproteinase-1 (TIMP-1) is able to prevent activation of pro-MMP-9 and forms a 1:1 complex with the active form of MMP-9. The aim of the present study was to investigate the expression of MMP-9 and TIMP-1 in benign, borderline, and invasive epithelial ovarian tumors. MATERIALS AND METHODS: A total of 90 patients with epithelial ovarian tumor were treated at the Brigham and Women's Hospital and were used as the study population. Immunohistochemistry and in situ hybridization were performed to detect protein and mRNA expression of MMP-9 and TIMP-1. RESULTS: In the 90 epithelial ovarian tumors tested, MMP-9 expression in tumor cells was found to be significantly enhanced in serous and mucinous ovarian carcinomas compared with benign and borderline tumors. We also observed the immunostaining of MMP-9 in stromal cells of benign, borderline, and invasive epithelial ovarian tumors. Moreover, the expression levels of TIMP-1 in tumor cells were significantly higher in borderline and invasive ovarian tumors than in benign tumors. CONCLUSION: Using an in situ hybridization technique, we disclosed a direct correlation between the presence of mRNA and protein expression for both MMP-9 and TIMP-1. The present data suggest that high levels of MMP-9 protein in invasive epithelial ovarian carcinoma are strongly associated with tumor cell invasion. Enhanced expression of TIMP-1 protein in borderline and invasive tumors indicates that endogenous TIMP-1 protein may play a paradoxical role in ovarian tumor progression.     

Current issues in the pathology of ovarian cancer

The majority of primary ovarian tumors are histologically classified as surface epithelial-stromal neoplasms. The malignant potential of such neoplasms may be categorized, on the basis of the extent of epithelial proliferation and stromal invasion, as benign, borderline or malignant. Recent efforts to further classify the malignant potential of such neoplasms have produced a new system for the histologic grading of ovarian carcinoma as well as new potential histologic predictors of behavior, including micropapillary morphology and stromal microinvasion in serous tumors. Among mucinous ovarian neoplasms, new criteria have been proposed to distinguish primary ovarian from metastatic carcinomas; the distinction may be difficult but has great clinical significance. The origin of ovarian mucinous tumors associated with pseudomyxoma peritonei has been reassessed. Finally, recent pathologic findings from prophylactic salpingo-oophorectomy specimens in patients with hereditary risks for ovarian carcinoma have highlighted the additional risk for fallopian tube carcinoma and primary peritoneal carcinoma. Special processing of the pathologic specimens is required to detect early and minimal neoplasia in this setting. These current issues in the pathology of ovarian carcinoma and their clinical significance form the basis of this review.     

Carcinosarcoma-like mural nodule in intestinal-type mucinous ovarian of borderline malignancy: a case report

Epithelial ovarian tumors of borderline malignancy are tumors with histologic features and biologic behavior between benign and frankly malignant epithelial ovarian neoplasms. To date, we cannot accurately predict the patients who are prone to an aggressive course of disease. Here, we present a 35-year-old patient with carcinosarcoma-like mural nodule in intestinal-type mucinous ovarian tumor of borderline malignancy. Foci of intraepithelial carcinoma (about 10%) without stromal invasion are also noted. Total hysterectomy, bilateral salpingo-oophorectomy, appendectomy, and omentectomy were performed, and the frozen pathology during operation showed mucinous tumor of borderline malignancy of left ovary on April 18, 2002. The patient was followed at our outpatient department for 19 months after operation and was free of the disease without any adjuvant chemotherapy. It is difficult to determine whether intestinal-type borderline mucinous tumors with intraepithelial carcinoma are associated with a worse prognosis compared with those with epithelial atypia alone due to disparate results in the published literature. In contrast, most patients with mural nodules of anaplastic carcinoma have had a malignant, often rapid, course. However, too few cases of carcinosarcoma-like mural nodule in mucinous tumor have been published to warrant a conclusion regarding their prognosis.     

Expression of mesothelin, fascin, and prostate stem cell antigen in primary ovarian mucinous tumors and their utility in differentiating primary ovarian mucinous tumors from metastatic pancreatic mucinous carcinomas in the ovary.

Metastatic pancreatic mucinous adenocarcinomas in the ovaries can be difficult to distinguish from primary ovarian mucinous neoplasms because the former can simulate the latter grossly and histologically and both tumor types share the same cytokeratin 7/cytokeratin 20 immunoprofile. We previously reported the utility of loss of Dpc4 expression in distinguishing metastatic pancreatic carcinomas from primary ovarian mucinous tumors. Recently several new pancreatic carcinoma markers have been identified, including mesothelin, fascin, and prostate stem cell antigen (PSCA). In this study we investigate the expression patterns of these markers in 35 primary ovarian mucinous tumors (28 atypical proliferative [borderline] tumors and 7 invasive carcinomas) and 11 metastatic pancreatic mucinous carcinomas in the ovary. Primary ovarian mucinous tumors expressed mesothelin (17%), fascin (26%), and PSCA (43%) less frequently than metastatic pancreatic adenocarcinomas (73%, 73%, and 82%, respectively). Expression of all three markers was seen only in metastatic pancreatic adenocarcinomas (45%), and coexpression of at least two markers was observed significantly more frequently in metastatic (82%) than primary ovarian mucinous tumors (17%). Our results indicate that an immunohistochemical panel including Dpc4, mesothelin, fascin, and PSCA is useful for evaluating difficult mucinous tumors in the ovary when the differential diagnosis includes metastatic pancreatic adenocarcinoma.     

卵巢上皮性肿瘤的临床病理特征及其细胞周期素D1和p53蛋白表达的研究

目的研究卵巢上皮性癌（卵巢癌）和交界性上皮性肿瘤的临床病理特征及其细胞周期素D1（cyclin D1）和p53蛋白表达的情况,探讨卵巢癌和交界性上皮性肿瘤在发病机制上的联系。方法分析45例卵巢癌（卵巢癌组）和54例卵巢交界性上皮性肿瘤（交界性肿瘤组）的临床病理资料,采用免疫组化法检测两组组织中cyclin D1、p53蛋白的表达情况,并分析其与临床病理特征的相关性。结果（1）临床病理特征：①年龄：交界性肿瘤组平均年龄为42．5岁（14～82岁）,中位数年龄41岁;卵巢癌组平均年龄为53．5岁（26～80岁）,中位数年龄51岁。②分期：按国际妇产科联盟（FIGO）分期标准,交界性肿瘤组Ⅰ期48例、Ⅱ期3例、Ⅲ期3例;卵巢癌组Ⅰ期6例、Ⅱ期8例、Ⅲ期26例、Ⅳ期5例。③病理类型：交界性肿瘤组以黏液型为主[占56％（30／54）],其次为浆液型[其中普通型11例,微乳头型5例;占30％（16／54）];卵巢癌组以浆液型（其中低度恶性19例,高度恶性3例）为主[占49％（22／45）]。④病理分化程度：卵巢癌组高分化5例,中分化17例,低分化或未分化23例。⑤预后：交界性肿瘤组5年生存率为98％,卵巢癌组为51％,两组比较,差异有统计学意义（P=0．000）。（2）cyclin D1和p53蛋白的表达及其与卵巢癌和交界性肿瘤临床病理特征的相关性：卵巢癌组cyclin D1和p53蛋白的阳性表达率分别为31％（14／45）和56％（25／45）,p53蛋白表达强度与病理分化程度呈正相关（r=0．320,P=0．032）;交界性肿瘤组cyclin D1和p53蛋白的阳性表达率分别为69％（37／54）和6％（3／54）。其中,普通型浆液性交界性肿瘤与高度恶性浆液性癌比较（两者cyclin D1蛋白阳性表达率分别为91％和26％,p53蛋白分别为0和58％）,差异有统计学意义（P〈O．01）;而微乳头型浆液性交界性肿瘤与低度恶性浆液癌比较（两者cyclin D1蛋白阳性表达率分别为3／5和2／3,p53蛋白分别为1／5和1／3）,差异则无统计学意义（P〉0．05）。结论cyclin D1蛋白的过度表达常见于卵巢浆液性交界性肿瘤及低度恶性浆液性癌组织中,而p53蛋白的过度表达更多见于高度恶性浆液性癌组织中。卵巢浆液性交界性肿瘤与高度恶性浆液性癌具有不同的发病机制,而微乳头型浆液性交界性肿瘤与低度恶性浆液性癌的关系可能更为密切。     

Multifocal tumorigenesis in the upper female genital tract--implications for staging and management

A review of 128 cases of "primary" ovarian müllerian carcinoma treated at the King George V Memorial Hospital was undertaken to determine the relative frequency with which such tumors were associated with evidence of multifocal primary neoplasia. Of the 128 cases studied, 115 were invasive carcinomas and 13 were noninvasive or borderline ovarian tumors ("tumors of low malignant potential"). Eight of 10 borderline serous ovarian tumors (80%) and 37 of 75 invasive serous carcinomas (49%) exhibited evidence of independent primary neoplasia at more than one anatomical site in the biopsy material available for review. Many of these cases represented bilateral primary ovarian tumors, but autochthonous extraovarian neoplasia was also commonly encountered. A single borderline endometrioid ovarian tumor and six of 15 endometrioid carcinomas (40%) were associated with biopsy-proven multifocal primary tumorigenesis. These were predominantly neoplasms in one or both ovaries plus adenocarcinoma in the uterine corpus. Other histological types of malignant common epithelial tumors of the ovaries did not demonstrate any such tendency, highlighting major differences in pathogenesis between members of this loosely associated group of ovarian cancers. Our study suggests that gynecological endometrioid and serous malignancies are commonly multifocal and we feel this has significant implications for the way these neoplasms are staged and therefore treated.     

Virilization in pregnancy due to a borderline mucinous ovarian tumor

Virilization in pregnancy due to borderline mucinous ovarian tumors is very rare. A case of a 28-year-old patient who was noted at 28 weeks' gestation to have marked virilization with raised serum androgens, ascites and a large complex right adnexal mass is presented. Delivery was carried out by cesarean section and at surgery a large tumor was noted in the right ovary. Histology revealed a borderline mucinous ovarian tumor with stromal luteinization, but there was no evidence of stromal invasion. Serum androgens returned to normal levels following surgery and the maternal virilization had resolved at the 6-week postnatal visit. Stromal changes in borderline mucinous ovarian tumors may result in virilization due to androgen production; surgical removal is associated with an excellent clinical outcome.     

KRAS and BRAF mutations in ovarian tumors: a comprehensive study of invasive carcinomas, borderline tumors and extraovarian implants

OBJECTIVE: Mutations of BRAF, a downstream mediator of K-RAS, have been described in serous borderline tumors of the ovary. Data concerning other types of ovarian tumors are scarce. Therefore, we assessed KRAS and BRAF mutation in a series of more than 100 different ovarian tumors. METHODS: Paraffin-embedded material, including invasive carcinomas, borderline tumors, benign lesions and implants, was used. BRAF codon 600 in exon 15 and K-RAS codon 12 in exon 2 were analysed. RESULTS: 92 cases (92%), including all serous carcinomas (100%), did not show a mutation of BRAF. Eight cases (8.0%), including five serous borderline tumors (31.25%), contained a mutation. In all serous borderline tumors, codon 600 was affected. The remaining three cases were invasive carcinomas of endometrioid (mutation on codon 600), mucinous (mutation on codon 600) and clear cell (mutation on codon 615) subtype. There was no BRAF mutation in mucinous borderline tumors. Regarding K-RAS, 89 cases (87.25%) did not show an aberration. The 11 positive borderline tumors (10.7%) were of serous (22.2%) and of mucinous type (46.6%). There was a KRAS mutation in a serous and a mucinous invasive carcinoma each. BRAF and K-RAS mutations were mutually exclusive and not seen in implants. CONCLUSION: Mutation of either K-RAS or BRAF is frequent in borderline tumors but is not found in invasive serous carcinomas and is very rare in other invasive subtypes. This supports the notion of different pathological pathways. For the development of extraovarian implants, further studies are observed.     

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.     

Role of KRAS and BRAF gene mutations in mucinous ovarian carcinoma

OBJECTIVES: The goals of this study were to perform a comprehensive assessment of the prevalence of KRAS oncogene mutations in invasive epithelial ovarian carcinomas of various histologic subtypes, and for any subgroup(s) in which KRAS mutation was found to be common, to address the hypothesis that those tumors without KRAS mutation had sustained alternative activation of this signaling pathway through mutation of the BRAF oncogene. METHODS: A total of 104 primary, invasive epithelial ovarian carcinomas from a 10-year period at this institution were selected for study based on histologic classification. The histologic cell type was serous in 21 cases, endometrioid in 30 cases, clear cell in 31 cases, and mucinous in 22 cases. Additional clinical and pathological information was abstracted from patient records, and pathology review was performed for all cases. Direct sequence analysis of exon 2 of the KRAS gene, containing codon 12, was performed using DNA isolated from all tumor specimens. Sequence analyses of exons 11 and 15 of the BRAF gene were performed for the 22 cases of mucinous ovarian carcinoma. RESULTS: Activating KRAS mutations were more common in mucinous tumors (50%) than in all other histologic types combined (5%; P < 10(-7)). Mutation of KRAS was more common in stage I tumors than in advanced stage tumors (P = 0.0004). Of the 11 mucinous tumors with KRAS mutations, 6 were of Mullerian (endocervical) type and 5 were of gastrointestinal type. No mucinous tumor was found to harbor a BRAF mutation. CONCLUSIONS: These data indicate that KRAS oncogene mutations exist in several histologic types of invasive epithelial ovarian carcinoma, especially stage I tumors, but are common only in tumors of mucinous histology. Mutations are equally prevalent in mucinous ovarian cancers of Müllerian and gastrointestinal types. In contrast to other solid tumor types frequently affected by KRAS mutation, mucinous ovarian cancers without a KRAS mutation have not sustained alternative activation of this signaling pathway through mutation of the BRAF oncogene.     

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.     

卵巢粘液性上皮内癌12例报告

目的:探讨卵巢粘液性上皮内癌的诊断意义和临床特点。方法:回顾分析2001年以来北京协和医院收治的12例卵巢粘液性上皮内癌(组织学检查确诊)的病理及临床特点和预后,并复习文献进行讨论。结果:患者中位年龄40.0岁。肿瘤均为单侧,肿瘤最大直径的中位数19.0cm(8.0~55.0cm)。ⅠA期8例,ⅠC期4例。1例行肿物剔除术,5例行附件切除术,3例行全子宫加双附件切除术,3例行肿瘤细胞减灭术。平均随诊38.8个月,无1例复发或死亡。结论:卵巢粘液性上皮内癌属卵巢粘液性交界瘤范畴,可能是浸润癌的癌前病变。年轻患者可行保留生育功能手术,预后较好,与同期别的粘液性交界瘤相当。     

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.     

Clinical characteristics and prognosis of mucinous tumors of the ovary

OBJECTIVE: Ovarian mucinous tumors consist of benign, borderline, and carcinomatous tumor, but the clinical characteristics of these 3 types have not been investigated in detail. In this study, we compared the clinical characteristics and prognosis among these 3 types of mucinous tumors. METHODS: One hundred sixty-one patients with mucinous cystadenocarcinoma and 143 patients with mucinous borderline tumor were registered between 1986 and 2003. All patients were reviewed by two pathologists, then the mixed type and cases showing other organized malignant tumors were excluded from this study. Patients with mucinous carcinoma staged Ib or more were treated postoperatively with 6 cycles of platinum-based chemotherapy. Survival probability was analyzed by the Kaplan-Meier method and differences in survival rates were calculated using log-rank test. RESULTS: Mean patient ages were 43.9, 44.7, and 49.7 years in patients with benign, borderline, carcinomatous tumor, respectively. The ratio of early stage (I, II) to advanced stage (III, IV) was significantly lower in carcinoma than in borderline tumor. The levels of tumor markers tended to increase with the level of malignancy. CA72-4 is the most useful discriminating marker according to ROC analysis. In borderline tumor, 5 patients died of disease, and all of these patients had stage III disease with residual tumor after the initial surgery. Patients with borderline tumor showed significantly better prognosis than those with carcinoma; however, there were no significant differences in prognosis between borderline tumor and carcinoma in patients with stage III tumor or residual tumor. CONCLUSIONS: In mucinous tumors, measurement of CA72-4 is recommended to distinguish malignant from benign tumors. Even in borderline tumor, patients with residual tumor showed a poorer prognosis than carcinoma, suggesting that complete resection is necessary for a good prognosis.