Correlation of multiple steroid receptors with histological type and grade in human ovarian cancer

One hundred eight human ovarian cancers were analyzed for estrogen (ER), progestin (PgR), and androgen (AR) receptors. The receptor levels were related to histological type and grade of the tumor. There were 103 common epithelial carcinomas subdivided into serous (36), endometrioid (36), mucinous (18), clear cell (5), malignant Brenner (3), mixed epithelial (2), and undifferentiated (3) types. Of the remaining five, four were sex cord-stromal tumors and there was a single case of germ cell tumor. ER was detected in 52%, PgR in 52%, and AR in 91% of the cases. There was no correlation between the presence of ER and AR and the tumor histology. The presence of PgR correlated with the grade of endometrioid carcinoma, while no clear correlation existed for the other tumor types. PgR was absent in the three undifferentiated carcinomas. Interestingly, high PgR levels were detected in the three granulosa cell tumors.     

Urothelial and ovarian carcinomas of identical cell types: problems in interpretation. A report of three cases and review of the literature

Three women, 51-69 years of age with carcinomas of the urinary bladder or ureter, had ovarian tumors of identical cell types 2 to 7 years apart. In two cases the tumors were transitional-cell carcinomas and in the third case, signet-ring-cell carcinomas. It was difficult in the cases of transitional-cell carcinoma to determine whether the ovarian tumors were metastatic or independent primary tumors. Consideration of a variety of features of our two cases and of four similar cases reported in the literature led us to the conclusion that the ovarian tumors were probably metastatic in one case, probably primary in two cases, and of unknown nature in three cases, but some degree of doubt existed in all the cases. The signet-ring-cell tumor in the ovary had the typical features of a Krukenberg tumor. Four of 11 women with signet-ring-cell carcinomas of the bladder have had ovarian metastases.     

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。     

Immunohistochemical demonstration of HNK-1-defined antigen in gynecologic tumors with argyrophilia

Gynecologic tumors with argyrophilia were tested immunohistochemically for reactivity with monoclonal antibody HNK-1, which detects normal and neoplastic cells derived from the neuroectodermal and the amine-precursor-uptake and decarboxylation (APUD) systems. The tumors included six small cell carcinomas and four adenocarcinomas of the cervix; 23 adenocarcinomas of the endometrium (13 with type I and 10 with type II argyrophil cells); and 11 mucinous tumors (three benign, three borderline, and five malignant), eight endometrioid carcinomas (four with type I and four with type II argyrophil cells), and two carcinoid tumors (one insular and one strumal) of the ovary. HNK-1 reactive cells were found in almost every category of tumor: in four small cell carcinomas and two adenocarcinomas of the cervix; 11 adenocarcinomas of the endometrium (eight with type I and three with type II argyrophil cells); and four mucinous (two benign and two borderline), two endometrioid (one with type I and one with type II argyrophil cells), and two carcinoid tumors of the ovary. These cells corresponded to at least some of the type I argyrophil cells in endometrial and ovarian endometrioid carcinomas and to similar cells in mucinous and carcinoid tumors of the ovary and small cell carcinoma and adenocarcinoma of the cervix. However, the remaining type I and similar argyrophil cells and almost all type II argyrophil cells were HNK-1 negative, and some of the nonargyrophil tumor cells were HNK-1 positive. Although the significance of such discrepancies in reactivity with HNK-1 antibody remains unknown, the present results suggest that some of the gynecologic tumors with argyrophilia are related to APUDomas.     

Serous psammocarcinoma of the ovary and peritoneum

We report 11 cases of serous psammocarcinoma, a rare variant of serous carcinoma characterized by massive psammoma body formation and low-grade cytological features. The patients ranged in age from 36 to 76 (mean of 57) years. The tumors were stage three in every case (three stage IIIA, seven stage IIIB, and one stage IIIC). Eight of the patients had ovarian psammocarcinomas with ovarian tumors measuring 5-22 (mean of 11) cm in diameter; the other three patients had primary peritoneal psammocarcinomas. The surfaces of the ovarian tumors were smooth and intact in seven of eight ovarian psammocarcinomas. Cysts were present in six of eight ovarian tumors, and the solid portions were typically gritty or granular. Necrosis was not seen. Microscopically there was destructive invasion of ovarian stroma or vascular invasion in the ovarian tumors; the extraovarian tumor implants were invasive of intraperitoneal viscera in five cases. The epithelium was arranged in small nests with no areas of solid epithelial proliferation, and at least 75% of the epithelial nests were associated with psammoma body formation. No more than moderate nuclear atypicality was identified in any case. No mitotic figures were found in 10 of the tumors, with a single mitotic figure identified in the other tumor. Follow-up data for more than 1 year was available for six patients, with two patients lost to follow-up and three patients followed without evidence of recurrence for less than 1 year. One patient died of tumor 6 1/2 years after presentation, and five patients were alive without evidence of recurrent tumor 3-10 (mean of 8.3) years after presentation. Although based on a small number of cases, these data suggest that the clinical behavior of psammocarcinoma more closely resembles that of borderline serous tumors than of serous carcinomas of the usual type, following a protracted course and being associated with a relatively favorable prognosis.     

Hepatocyte paraffin 1 antibody does not distinguish primary ovarian tumors with hepatoid differentiation from metastatic hepatocellular carcinoma.

Anti-hepatocyte antibody, hepatocyte paraffin 1, is a monoclonal antibody that is highly specific for normal and neoplastic hepatocytes and that can differentiate hepatocytic from nonhepatocytic tumors. This marker has been rarely studied in extra-hepatic tumors and to our knowledge has not been investigated in ovarian tumors with hepatoid differentiation. We studied hepatocyte paraffin 1 immunoreactivity in a series of ovarian hepatoid carcinomas, ovarian hepatoid yolk sac tumors (YSTs), and hepatocellular carcinomas metastatic to the ovary to assess the potential utility of hepatocyte paraffin 1 in differential diagnosis. Hepatocyte paraffin 1 positivity was seen in three of seven ovarian hepatoid carcinomas, five of eight hepatoid yolk sac tumors, and six of eight metastatic hepatocellular carcinomas. The extent of positivity ranged from <25% to >50% of the tumor cells. There was strong coarsely granular cytoplasmic staining in all three tumor types without a distinctive staining pattern in any group. The degree of hepatic differentiation correlated with hepatocyte paraffin 1 positivity in the three groups: 83% of the well differentiated tumors, 50% of the moderately differentiated tumors, and none of the poorly differentiated tumors were positive. All ovarian hepatoid carcinomas were either immunoreactive for alpha-fetoprotein or had an elevated serum alpha-fetoprotein level; more than half of these tumors were hepatocyte paraffin 1 negative. All but one hepatocyte paraffin 1 negative hepatoid yolk sac tumor and ovarian hepatocellular carcinoma were also negative for alpha-fetoprotein. In conclusion, hepatocyte paraffin 1 is positive in primary ovarian tumors with hepatoid differentiation, with the degree of hepatocyte paraffin 1 positivity correlating with the degree of hepatoid differentiation. Hepatocyte paraffin 1, however, is not useful in distinguishing metastatic hepatocellular carcinoma from primary ovarian hepatoid carcinoma or hepatoid yolk sac tumor.     

Ovarian carcinoma during pregnancy: A study of 23 cases in Israel between the years 1960 and 1984

Data from a study on malignant ovarian tumors in pregnancy in Israel are presented. During the 25-year period of the survey, 23 new cases of malignant ovarian tumors during pregnancy were diagnosed, representing an incidence of 0.12/100,000 females over the age of 14; over half of the patients were in their third decade of life at the time of diagnosis of the tumor. Ovarian malignant tumors during pregnancy are more prevalent in Jewish women of European-American origin than in those of Asian-African descent. Borderline carcinomas were found in 35% of our patients; epithelial invasive tumors were found in 30%; the other tumors were dysgerminoma (17%), granulosa cell tumor (13%), and undifferentiated carcinoma (5%). Most of the patients (74%) were diagnosed in stage I. In three cases, ovarian cancer was diagnosed during surgery for tubal pregnancy, and in two during cesarean section at term. In early-stage disease and low-potential-malignancy tumors, surgery can be conservative; thus, 14 of 23 bore a live child. In advanced disease, aggressive surgery, chemotherapy, and/or radiotherapy should be instituted. Factors affecting prognosis were age of patient, histologic type of tumor, and clinical stage of disease. Overall, the survival is much better than that for ovarian tumors in general, because most of the tumors are of low potential malignancy and are diagnosed at an early stage.     

The histologic type and stage distribution of ovarian carcinomas of surface epithelial origin.

Advances over the past decade suggest a need to reassess the distribution of ovarian surface epithelial tumors. A series of 220 consecutive invasive ovarian carcinomas, including carcinosarcomas and peritoneal carcinomas, was reviewed. Notable findings include: 7% of tumors were carcinosarcomas; 22% of cases of peritoneal serous carcinomatosis were of peritoneal origin; <3% of cases were mucinous carcinomas; and only one malignant Brenner tumor (0.5%) and no pure transitional cell carcinomas were identified. If peritoneal carcinomas, carcinosarcomas, and mixed carcinomas with a serous component are combined with serous carcinomas, this group accounts for 78% of all cases and 87% of advanced stage cases, suggesting a greater uniformity to epithelial ovarian cancer than previously appreciated.     

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.     

p21: a monitor of p53 dysfunction in ovarian neoplasia

p53 is an important tumor suppressor gene which is activated in response to DNA damage. The induced expression of p53 causes either cell cycle G1 arrest or apoptosis. The recently cloned p21 gene (WAF1/CIP1/SDI1) is known to be directly activated by wild-type but not mutant p53 and can suppress the growth of human cells in G1 by inhibiting the activity of cyclin-dependent kinases (CDKs). As p21 is activated by p53 and is a negative regulator of the cell cycle, it is possible that p21 could be a sensitive marker to monitor p53 function. To investigate the mRNA expression level and mutation status of p53 and p21 genes, quantitative polymerase chain reaction (PCR) and direct cDNA sequence analysis were performed. mRNA expression levels of p53 and p21 genes relative to the β-tubulin gene were examined in 32 ovarian tumors (24 carcinomas, six low malignant potentials (LMPs), two benigns) and six normal ovaries. Of 13 ovarian tumors with p21 underexpression, nine p53 mutated cases (69%) and one polymorphism case were found. Among nine p53 mutated cases, three cases showed p53 overexpression, another three cases showed p53 underexpression and a further three cases showed normal expression of p53. These findings suggest that mRNA underexpression of p21 may be a more useful indicator of p53 dysfunction than mRNA expression of p53.     

Adenocarcinomas arising from uterine adenomyosis: a report of four cases.

Adenocarcinomas arising from adenomyosis uteri are rare. This study reports four such cases and characterizes them clinically and microscopically. In all four patients, the endometrial cytology was negative, and MR imaging and ultrasound sonography did not detect the tumors preoperatively. The histological subtypes of the four tumors were endometrioid (one grade 1, one grade 3), serous, and clear cell. In three cases, the adenocarcinomas were present exclusively in the myometrium, and a transition between the carcinomas and the adenomyotic glands was observed in all cases. The eutopic endometrium was normal except in one case in which there was a small focus of invasive carcinoma. In two of four cases, pelvic or paraaortic lymph node metastases were present. In the carcinomas, ER immunoreactivity was not found in any tumor and PR positivity was found in only one tumor. In contrast, p53 immunopositivity was found in three of four carcinomas. Adenocarcinomas arising from adenomyosis are difficult to diagnose preoperatively, and their aggressive behavior in some cases seems to be related to the histological subtype.     

In vitro chemoresistance and biomarker profiles are unique for histologic subtypes of epithelial ovarian cancer

OBJECTIVES: To determine whether there is a relationship between histologic subtype of epithelial ovarian cancer and chemoresistance, we evaluated ovarian carcinomas of six histologic subtypes and correlated histology with in vitro drug response. Biomarker profiles (p53, Her-2 neu, and EGFR) were also evaluated to determine if their expression patterns were associated with histology. METHODS: In vitro drug response profiles for different histologic subsets of epithelial ovarian carcinomas exposed to standard relevant chemotherapy agents were determined in the Extreme Drug Resistance assay (EDR). Immunohistochemistry techniques were employed to determine biomarker expression. RESULTS: Of 5195 referred serial cases of epithelial ovarian cancer, there were 2660 papillary serous, 303 endometrioid, 142 mucinous, 102 clear cell, 952 undifferentiated carcinomas, and 42 tumors of low malignant potential. For the samples as a whole, the incidences of extreme drug resistance to the tested chemotherapeutic agents were cisplatin 10%, carboplatin 16%, cyclophosphamide 16%, doxorubicin 40%, gemcitabine 21%, paclitaxel 22%, and topotecan 13%. When compared to papillary serous tumors, mucinous tumors were more frequently resistant to cisplatin (10% vs. 18%) but less frequently resistant to topotecan (13% vs. 5%) and doxorubicin (42% vs. 16%). Endometrioid tumors were less resistant to cisplatin (10% vs. 6%) and doxorubicin (42% vs. 20%). Clear cell and undifferentiated tumors had the lowest rates of EDR to paclitaxel (13% and 18%) and cyclophosphamide (7% and 11%), while borderline tumors showed high rates of EDR to these agents (52% and 63%, respectively). With respect to biomarker profiles, mP53 was detected in 46%, Her-2 neu in 16%, and EGFR in 30% of the cases evaluated. As compared to all other subtypes, clear cell carcinomas had significantly higher Her-2 neu expression (19%). Relative to papillary serous carcinomas, borderline tumors exhibited significantly lower rates of mP53 expression (60% vs.17%). CONCLUSIONS: We found significant differences in the frequencies of extreme drug resistance to chemotherapeutic agents and biomarker expression among histologic subtypes of epithelial ovarian cancer. The data collected in this investigation may provide a guide for stratification of patients entering clinical trials based on histology and biomarker expression.     

Flow cytometric DNA analysis of ovarian Brenner tumors and transitional cell carcinomas.

Flow cytometry has been previously used as a method of obtaining prognostic information about ovarian carcinomas using ploidy, DNA index, and S-phase fraction. DNA content has also been assessed in ovarian tumors of low malignant potential. Brenner tumor variants such as metaplastic, proliferating, and low malignant potential, recently designated as intermediate Brenner tumors, and malignant Brenner tumors are unusual tumors that present classification problems. Their histological appearance may not accurately reflect biological activity. We used flow cytometry to analyze paraffin-embedded tissue for DNA content and S-phase in 34 Brenner tumors, three ovarian transitional cell (urothelial) carcinomas (TCCs), and nine normal control ovaries. We correlated histological and clinical features with DNA analysis. Twenty-five Brenner tumors and three ovarian TCCs were acceptable for histogram analysis (coefficient of variation less than 7.0). Thirteen typical, three metaplastic (extensive mucinous or glandular metaplasia), and two proliferating (papillary formation with increased cellularity) Brenner tumors were diploid. One proliferating tumor was tetraploid. The single Brenner tumor of low malignant potential was diploid but had an increased S-phase. Four of five malignant Brenner tumors were aneuploid, and one was diploid. All the TCCs were aneuploid. S-phase was elevated in intermediate and malignant Brenner tumors and TCC. Limited numbers of cases available preclude prognostic prediction based on ploidy in malignant Brenner tumors or primary ovarian TCCs. DNA ploidy and S-phase reflect the intermediate status of metaplastic, proliferating, and low malignant potential Brenner tumors.     

Endocrinological and clinico-pathologic study of granulosa-theca cell tumors of the ovary

Nine granulosa-theca cell tumors (four pure theca cell tumors, one granulosa cell tumors, two granulosa-theca tumors and two juvenile granulosa-theca tumors) were studied endocrinologically and clinico-pathologically. The cases of juvenile granulosa-theca tumors developed precocious pseudopuberty. Three of seven other cases were re-feminized and four cases showed no hormonal manifestation clinically. The peripheral vein serum values of estradiol, progesterone, testosterone and prolactin were elevated in six of eight cases, three of four cases, four of six cases, and two of three cases, respectively. The concentration ratios between tumor harboring ovarian vein samples and peripheral vein (or opposite normal ovarian vein) samples was 2.7 to 16.9 for estrone, 8.8 to 28.6 for estradiol, 3.6 to 4.7 for progesterone, 1.6 to 6.6 for testosterone and 0.6 to 1.0 for prolactin. Estradiol was localized in both granulosa cells and theca cells, and testosterone was localized in granulosa cells in half of the cases and in theca cells in 60% of the cases. Also, testosterone was localized in all three cases in which luteinized theca cells were present. There were no cases with positive prolactin localization. These results are compatible with the concept that in granulosa-theca cell tumor, both granulosa and theca cells can produce a wide range of steroid hormones.     

Dysgerminoma in a patient with a tumor of the neck. Empiric treatment of stage IV dysgerminoma

The evolution of therapy for malignant ovarian germ cell tumors is one of the true success stories in oncology. Treatment outcome has improved greatly thanks to cisplatin-based combination chemotherapy. According to the well-established treatment guidelines for advanced cases, we treated a case of stage IV undifferentiated germ cell tumor in which we were able to preserve the patient's fertility. We concluded that the PEP regimen is an effective treatment for the patient with metastatic germ cell tumor.     

Laparoscopic treatment of ovarian tumors in children: an experience of seven cases in Mansoura University Hospital

All ovarian tumors in children are rare. Laparoscopic ovary-sparing treatment of ovarian tumor would be the preferred surgical approach for children in order to preserve future fertility. The objective of this research is to study the experience of gynecology department in Mansoura University Hospital in laparoscopic treatment of ovarian tumors in children. This study included seven patients with age range of 7 to 11 years presented with ovarian tumors. The following items were fulfilled for all studied cases: age at diagnosis, presenting complaints, blood samples for detection of tumor markers, abdominal ultrasonography, abdominal magnetic resonance imaging (MRI), treatment by laparoscopy, histopathological examination, and the outcome of the patients. All ovarian tumors were benign. Three cases were found to be cystic teratomas, two cases were benign serous cystadenoma, only one case was cystadeno-fibroma and one case was solid tumor, and its histology did not give a clear diagnosis, but no malignant cells were found. Unilateral salpingo-oophorectomy was carried out in three patients, whereas the other four patients had unilateral ovarian cystectomy. In one case, intraoperative spillage during excision of the tumoroccurred. Recovery of all patients was good and without any complications. Laparoscopic conservative surgery as a treatment for benign ovarian tumor in childhood gives a good chance to preserve future fertility.     

Sebaceous tumors arising in ovarian dermoid cysts.

The clinicopathologic features of five cases of sebaceous tumors arising in ovarian dermoid cysts and of three previously reported cases are reviewed. They occurred in women with an average age of 58 years and were classified as sebaceous adenoma (five cases), basal cell carcinoma with sebaceous differentiation (two cases), and sebaceous carcinoma (one case). Follow-up information was available for all cases. One patient with basal cell carcinoma with sebaceous differentiation had a pelvic recurrence 2 1/2 years after diagnosis. In no other case did the sebaceous tumor recur or metastasize during follow-up periods of 1 to 6 years. One patient died of a squamous cell carcinoma that arose in the same dermoid cyst as the sebaceous tumor. These tumors represent a rare form of monodermal neoplasia in dermoid cysts.     

Small cell carcinoma of the ovary. A report of six cases

Six cases of small cell carcinoma of the ovary are presented. The tumors occurred in women with an average age of 27.5 years. According to the International Federation of Gynecology and Obstetrics (FIGO), two patients had Stage I, three Stage II, and one Stage III disease. The tumors behaved highly malignantly, as four of the patients died from disseminated disease within 20 months. Three of the tumors were found to be associated with elevated serum calcium levels. By light microscopy three of the tumors were originally misinterpreted: one as an undifferentiated tumor, probably of stromal origin; one as a germ cell tumor, probably endodermal sinus tumor; and the third as a granulosa cell tumor. In four tumors examined by electron microscopy, the epithelial nature was confirmed, and three of them contained neuroendocrine granules. Immunocytochemical examination in five cases revealed positive staining for neuron-specific enolase (NSE) and negative staining for beta 2-microglobulin, whereas one case was negative for NSE and positive for beta 2-microglobulin. A positive immunoreaction for parathyroid hormone was observed in three cases (all NSE positive). In two of these a raised serum calcium level was documented. This finding possibly gives a clue to the hypercalcemia so frequently found in these patients.     

Expression P53 protein and chromosome aberrations in benign tumors and ovarian carcinoma

OBJECTIVES: The epithelial ovarian tumors arise from the single layer of epithelial cells that line the ovarian surface or from underlying inclusion cysts. One from many theories of oncogenesis has been proposed that benign, borderline and invasive tumors represent sequential stages in the growth of an ovarian cancer, and p53 tumor suppressor gene mutation is the most common molecular genetic alteration. Because locus of p53 gene is located on 17 chromosome we performed the cytogenic analysis of tumor tissues. DESIGN: Analysis of mutated p53 protein expression and chromosomal aberrations in tissues of benign tumors and epithelial ovarian carcinomas. MATERIAL AND METHODS: Tissue samples from 19 women with benign and 17 women with invasive epithelial ovarian cancers were obtained for the study at the time of surgical procedures. From among benign tumors 12 were serous cystadenomas, 5 were endometrial cysts and 2 adult teratomas. All cases of invasive epithelial ovarian carcinomas were histologically recognized as serous adenocarcinomas, and were staged on I (9 cases), II (5 cases) and III (3 cases), according to the FIGO guidelines for ovarian cancers. Frozen tissue samples were stained immunohistochemically for mutated p53 protein using commercial monoclonal antibodies and standard detecting system. The fresh tumor samples were prepared for cytogenic analysis according to standard protocol. RESULTS: Among the all benign ovarian tumors overexpression of mutated form of p53 protein was not seen in any cases, but was noted in 6 cases in I stage and in all cases in II and III stages of advanced ovarian cancers. In 1 case of benign ovarian tumor deletion of X chromosome was observed. Most common numerical changes were observed in ovarian carcinomas e.g. loss of 8, 13, 17, and 22 chromosomes. Other chromosomes were involved at least once in structural rearrangements and several breakpoint cluster regions were identified: 19p13, 11p13-15, 1q21-23, 1p36, 19q13, and 6q21-23. CONCLUSIONS: The mutated form of p53 protein is often expressed in ovarian epithelial carcinoma tissues. This protein are unable to function effectively to inhibit proliferation and accumulate in the cells because is resistant to degradation. In tissues of ovarian carcinomas many chromosomal nondisjunctions (monosomics) and multiple structural rearrangements were observed, what means of genetically nonstable cell lines of neoplasms and probably it heterogenous origin.     

Ovarian mixed-epithelial carcinomas with a microcystic pattern and signet-ring cells.

Primary ovarian carcinomas with unusual histologic patterns can be difficult to differentiate from metastases. In this study, we reviewed 15 cases of mixed-epithelial carcinoma (12 serous, 1 serous and endometrioid, 1 endometrioid, 1 undifferentiated) with a predominant microcystic pattern and signet-ring cells. The patients' ages ranged from 31 to 78 (mean 58) years. The microcystic component in 11 patients had features of high-grade carcinoma and in 4 patients had features of low-grade carcinoma associated with areas of borderline tumor. The tumors in all 15 patients showed a predominant microcystic growth pattern composed of small cysts that were variable in size and shape. Signet-ring cells were also present in all cases (diffusely in nine cases, focally in six cases) within the neoplastic epithelial proliferation. Mucin was present in the lumina of some of the microcysts and in the cytoplasm of most of the signet-ring cells. A microcystic pattern and mucin-containing signet-ring cells can be seen as small foci or as a predominant component in primary epithelial nonmucinous ovarian carcinomas. It is important for pathologists to recognize these unusual findings in ovarian neoplasms, because they may produce a confusing apperance, even potentially suggesting a metastasis.