Histochemical study of mucinous ovarian cystomas of intestinal and mixed types: O-acetylated sialomucin content in relation to biologic behavior.

The subgroup of mucinous ovarian cystomas of intestinal type containing site 8 O-acetylated sialomucins and its relation to malignant behavior were studied. Of 75 mucinous cystomas of the ovary from the files of the Institute of Pathological Anatomy and Histology (University of Genoa), 54 were endocervical, 19 were mixed, and 2 were intestinal. As regards their histologic pattern, the 54 mucinous endocervical cystomas were benign, whereas the 19 mixed type group included 8 benign, 5 borderline and 6 malignant; the 2 intestinal type tumors were borderline. According to histochemical investigations, the frequency of tumors with goblet cells containing site 8 O-acetylated sialomucins (positive to PB/KOH/PAS) was 47% in the mixed type cystomas and 100% in the intestinal type cystomas. Twenty-five percent of benign mixed cystomas, 60% of borderline mixed cystomas, and 67% of mixed cystadenocarcinomas were positive to PB/KOH/PAS. One hundred percent of the borderline cystomas of intestinal type were positive. Our results confirm that among mucinous ovarian cystomas, those containing intestinal type epithelium are the most likely to fall within the borderline or malignant categories. Moreover, of all ovarian cystomas of intestinal type, those characterized by site 8 O-acetylated sialomucins seem to be more aggressive and, in general, to have a more malignant behavior than the mucinous cystic tumors of müllerian or endocervical type.

Biochemical characterization of glycoprotein components in human ovarian cyst fluids by lectins.

1. Perchloric acid-soluble glycoprotein fractions (PASFs) were separated, in yields of 180-610 mg per 100 ml of cyst fluid, from the cyst fluids of human ovarian cystadenomas (OCAs) in benign and borderline and ovarian clear cell carcinoma (OCC) in malignant, and then identified as glycoproteins with 19.1-69.5% carbohydrate by their chemical composition analyses. 2. These PASFs reacted with anti-A, -B, -Lea and/or -Leb sera, but did not react with anti-H, -M and -N sera. All of the PASFs reacted with Ricinus communis lectin (RCA-I). Among these PASFs, PASFs from the cyst fluids of OCA in benign did not react with Arachis hypogaea anti-T lectin (PNA) and both of the anti-N lectins of Vicia graminea (VGA) and Vicia unijuga (VUA), and PASFs from OCA in borderline reacted with only PNA and PASFs from OCC in malignant reacted with the three lectins, PNA, VGA and VUA. However, none of PASFs from human normal sera and various normal organ tissues reacted with any of RCA, PNA, VGA and VUA. 3. The above-mentioned results seem to show that the examination of glycoproteins of ovarian cyst fluids by the combined use of RCA-I, PNA and VGA (or VUA) permits biochemical diagnosis of the canceration degree of ovarian cystomas.

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.

Tumor markers of epithelial ovarian neoplasms.

Ninety-three formalin-fixed, paraffin-embedded surgical specimens from 69 ovarian tumors representing all five epithelial cell types were studied by immunohistochemistry, peanut and ulex lectin binding, and carbohydrate histochemistry. Carcinoembryonic antigen (CEA) was mostly noticeable in mucinous tumors (21 of 26). Glycogen was highly prevalent in clear cell (8 of 9) and endometrioid (4 of 6) carcinomas, in contrast to serous carcinomas (3 of 6), where it was only focally distributed, and was completely absent in all mucinous tumors. Among the different types of malignant tumors examined, mucinous carcinomas most frequently contained neutral mucins (6 of 8). In mucinous tumors, an increase in CEA content and a decrease in the total mucin secretion, particularly the strongly acidic sulfated group, were found to parallel the increased malignant potential of the tumor. Peanut and/or ulex lectin binding was a feature common to almost all epithelial neoplasms. Although peanut lectin showed a slightly higher affinity to serous and clear cell tumors, while ulex lectin was bound more to mucinous and endometrioid neoplasms, distribution of D-galactose and L-fucose does not have a diagnostic utility in these tumors. Placental lactogen was detected in 3 of 17 benign tumors and one of 19 tumors of low malignant potential (LMP). The beta subunit of hCG was found in one of 17 benign tumors, in 2 of 19 LMP tumors, and in 3 of 31 carcinomas.

Localization of gonadotropin binding sites in human ovarian neoplasms.

The binding of human luteinizing hormone and human follicle-stimulating hormone to ovarian tumor biopsy specimens from 29 patients was analyzed. The binding sites for human luteinizing hormone were demonstrated in one tumor of epithelial origin (mucinous cystadenoma) and in one of sex cord-stromal origin (theca cell tumor). The binding sites for human follicle-stimulating hormone were found in three tumors of epithelial origin (serous cystadenoma and mucinous cystadenoma) and in two of sex cord-stromal origin (theca cell tumor and theca-granulosa cell tumor). The surface-binding autoradiographic study revealed that the binding sites for gonadotropins were localized in the stromal tissue. The results suggest that gonadotropic hormones may play a role in the growth and differentiation of a certain type of human ovarian neoplasms.

Papillary adenoma of the stomach. Pathologic and immunohistochemical study.

A total of 13 gastric papillary adenomas composed of 8 papillary and 5 papillotubular adenomas were examined pathologically and immunohistochemically. They showed a dome-like or pedunculated appearance and were located at the antrum, except for one adenoma. Histologically, the adenoma cells showed atypia in varying degree and focal adenocarcinoma was noted in seven lesions. The number of goblet cells was apparently smaller in the papillary than in the tubular portion. Lysozyme was present at the supranuclear region in most papillary adenoma cells, whereas it was concentrated in Paneth's granules in tubular adenoma cells. No difference was found in the distribution and frequency of carcinoembryonic antigen, secretory component, and carbohydrate antigen CA 19-9 between papillary and tubular adenomas. Paucity of endocrine cells also characterized gastric papillary adenoma. Different phenotypic expressions might reflect the difference in histogenesis between papillary adenoma and tubular adenoma.

[Mucin histochemical and immunohistochemical studies of mucinous ovarian tumors].

Mucinous ovarian tumors, (32 benign, 5 borderline, and 30 malignant) were studied by using mucin histochemical staining and immunohistochemical method. Results showed that neutral and acid mucoproteins were demonstrated in these tumors; but their proportion and distribution were different. For instance, sulfuric acid mucoprotein was found in 12/32 (37.5%) of mucinous cystadenomas and in 25/30 (83.3%) of mucinous cystadenocarcinomas (P less than 0.01). Immunohistochemically, colon-ovarian tumor antigen (COTA) was 100% positive in malignant and borderline cases respectively but only 6/32 (18.8%) in the benign. The differences were statistically significant (P less than 0.01). Meanwhile, the differences between COTA staining and HID/AB staining for cystadenocarcinomas were also significant (P less than 0.05). These data suggest that COTA is more sensitive and specific antigen for mucinous ovarian tumors and may be useful for the early detection of malignant changes of mucinous ovarian tumors.

[Histogenetic considerations on mucinous cystomas of the ovary based on histochemical and immunohistochemical findings]. / Considerazioni istogenetiche sui cistomi mucinosi dell'ovaio in base a rilievi istochimici ed immunoistochimici.

Mucinous cystomas of the ovary, according to a new proposed classification (I.A.P., Dublin 1988), are classified in three types: endocervical, intestinal and mixed. Their histogenesis is still controversial, thus requiring further investigations. There are two main theories on this matter: a teratomatous theory based on the assumption that the mucinous cystoma is allegedly a teratoma having a monophyletic development where only the endodermal gastrointestinal component remains. The second theory, currently the most widely accepted one, maintains that mucinous cystomas derive from Muller duct residues or, more generally, from introflections of the coelomic epithelial lining through a Muller-type metaplastic process. Some authors also accept both theories. A group of 117 mucinous cystomas were investigated by histochemical methods (PB/KOH/PAS; PAT/KOH/Bh/PAS), to demonstrate the presence of O-acetylated sialomucin variants in goblet cells of intestinal type component. Endocervical type mucinous cystomas have always presented as PB/KOH/PAS negative, whereas mixed type mucinous cystomas presented as positive according to the following percentage: benign forms, 31%; borderline, 67%; malignant, 50%. These data should confirm the hypothesis that intestinal type cystomas may derive from the surface coelomic epithelium of the ovary, through a gastrointestinal metaplastic process. This hypothesis is further supported by the data obtained from the observation on two cases of intestinal metaplasia of endocervical glands, kindly supplied by Dr. Trowell. In one of them, a weak O-acetylated sialomucin secretion was identified, in addition to the presence of argentaffin cells. Furthermore, out of 38 adenocarcinomas of the endometrium and 15 adenocarcinomas of the endocervix, one case of endocervical adenocarcinoma was found, characterized by a mucous secretion rich in O-acetylated sialomucins. Moreover, immunohistochemically, by means of anti-chromogranin A monoclonal antibodies, endocrine cells were found in benign, borderline and malignant mucinous cystomas of mixed type. These data do not seem to confirm the assumed correlation between neuroendocrine cell presence and biologic behaviour of the neoplasm nor do they clarify tumor histogenesis. Another immunohistochemical study with BD5 monoclonal antibody demonstrated that this marker was present in the intestinal type epithelium of mixed mucinous cystomas. The histogenetic teratomatous hypothesis of ovarian mucinous cystomas was confirmed by reviewing 100 ovarian teratomas, in which O-acetylated sialomucins were found in the epithelial component of one mucinous carcinoid and in the intestinal type epithelium of 9 mature cystic teratomas.(ABSTRACT TRUNCATED AT 400 WORDS)

[Distribution of lectin-receptors in ovarian cystadenoma and cystadenocarcinoma].

55 cases of ovarian cystadenoma and cystadenocarcinoma were investigated with a panel of twelve various lectins and ABC technique. Results showed that RCA and WGA reacted with all the tumors, indicating that these two lectins are possibly functional differential markers of both ovarian mucinous and serous tumors. LCA, DBA and SJA might be of considerable help in differential diagnosis of serous cystadenoma and cystadenocarcinoma. PSA probably was a marker indicating malignant change of mucinous cystadenmas. Since there were different reactivities in mucinous and serous cystadenoma, SJA, DBA and SBA might be considered as the functional markers in differentiating these two different types of ovarian cystadenoma.

[Ganglioside content and profile in the ovarian tumor tissues and in the biological body fluids of patients]. / Soderzhanie i profil' gangliozidov v tkaniakh opukholei iaichnikov i biologicheskikh zhidkostiakh organizma bol'nykh.

Lipid-bound sialic acid (LSA) content and ganglioside composition in resected tumours and body fluids of patients with benign ovarian tumours, borderline ovarian tumours, ovarian cancer and also in unaltered ovaries of patients with uterine cancer were examined. LSA levels in tissues and relation of the main gangliosides GD3/GM3 progressively decreased from unaltered ovaries to ovarian cancer. Distribution of gangliosides GD3 and GM3 in the borderline tumours was not uniform. Absolute content of GD3 increased more than twice in profuse growth from the inner surface and decreased almost three times in the cyst capsule as compared to the intact tumour. Ganglioside GD3 content decreased in malignant ovarian tumours but increased in ascitic fluid of cancer patients as compared to GM3. These results suggest that ganglioside GD3 is shed more intensively in the borderline ovarian tumours.

Oral contraceptives and intrahepatic biliary cystadenoma having an increased level of estrogen receptor.

We report a case of intrahepatic biliary cystadenoma in a young woman who had no prior history of liver disease and who had taken oral contraceptives for one year. A 27-year-old woman was admitted to our hospital with a firm epigastric mass. At laparotomy, a large cystic mass was resected from the left hepatic lobe, and diagnosed as biliary cystadenoma. In the tumor tissue, the estrogen receptor content was 14.0 fmol/mg cytosol protein, which was much higher than the 3.0 fmol/mg cytosol protein in the surrounding liver tissue. This is the first case of biliary cystadenoma in which the estrogen receptor content was increased.

PIP: A 27-year-old woman with a 1-year history of oral contraceptive (OC) use presented to a Japanese medical center with a firm epigastric mass. The patient had no prior history of liver disease. Biliary cystadenoma was diagnosed on the basis of the cystic nature of the mass, several mural nodules, and the presence of large amounts of mucinous fluid. At laparotomy, a cystic mass 7.2 x 5.8 x 6.2 cm was rejected from the left hepatic lobe. Several smaller cysts, lined by a layer of columnar mucinous epithelium, were contained within the wall of the larger cyst. The estrogen receptor content of the tumor tissue was 14 fmol/mg cytosol protein compared to less than 3 fmol/mg in the surrounding liver tissue. Biliary cystadenoma accounts for under 5% of all solitary cysts of biliary origin. This is the 4th known case of such a tumor in an OC user. Although the precise etiology of this woman's biliary cystadenoma cannot be ascertained, the high estrogen receptor content in her cystadenoma suggests that these tumors are sensitive to estrogen and that estrogen-containing OCs may serve as tumor promoters.

Coexpression of cytokeratins and vimentin in common epithelial tumours of the ovary: an immunocytochemical study of eighty-three cases.

An immunocytochemical investigation has been performed on 83 common epithelial tumours of the ovary, to ascertain their capability of expressing vimentin in addition to cytokeratins. Our results demonstrate that vimentin coexpression is related to the tumour histotype and -to a lesser extent- to the degree of differentiation of malignant variants. Indeed, most serous tumours (80%), some endometrioid adenocarcinomas, and all the clear cell carcinomas investigated exhibited a variable number of neoplastic cells co-synthesizing the two distinct intermediate filament (IF) proteins, whereas only one of 29 mucinous tumours and none of the Brenner tumours displayed vimentin-immunoreactive cells. Moreover, in serous and endometrioid carcinomas, the expression of vimentin was related to the degree of tumour differentiation, being consistently identifiable in the better differentiated cases. The immunocytochemical findings of a parallel investigation on IF expression in the ovarian coelomic epithelium and in the müllerian-derived epithelia of the female genital tract allowed us to ascertain that ovarian epithelial tumours (with the possible exception of poorly differentiated carcinomas) maintain the pattern of IF expression typical of the normal epithelia. This investigation emphasizes the usefulness of IF typing as a tool for the more precise characterization of the origin and differentiation of human neoplasms.

Immunochemical characterization and radioimmunometric detection of molecules shed by human ovarian cancer.

Monoclonal antibodies (MAbs) OC125, MOv2 and MOv8 recognize the CA125, CAMOv2 and CAMOv8 epitopes, respectively, which are associated with human ovarian carcinomas and are shed by these tumors. The biochemical analysis of the recognized antigens and epitopes has been performed to investigate the possibility of exploiting their expression, if any, on the same molecules. Cross-competition experiments clearly indicated that the 3 epitopes are distinct. Biochemical analysis was performed on a cyst fluid from an ovarian cystadenoma. Heat treatment and periodate oxidation indicated that CAMOv2 and CAMOv8 are saccharidic and suggested that CA125 is a conformational epitope to which both saccharides and the protein backbone could contribute. By gel-filtration chromatography CA125 activity was eluted into 2 peaks of high molecular weight, whereas CAMOv2 and CAMOv8 activities were associated with a single broad peak which included CA125-positive fractions. Isopycnic centrifugation showed that CA125, CAMOv2 and CAMOv8 carrying molecules had the same high density (1.46 g/ml) in the first peak, whereas CA125 molecules had a lower density (1.41 g/ml) in the second peak. Double-determinant immunoradiometric assays, carried out using different combinations of the MAbs, indicated that in the cyst fluid molecules expressing both CAMOv2 and CAMOv8 could be detected, whereas CA125 was carried by different molecules. CAMOv2 and CA125 could however be expressed on the same molecule in 2 out of 9 ascitic fluids from ovarian carcinoma patients. Taken together, these data indicate that CA125 and CAMOv2-CAMOv8 were only occasionally expressed on the same molecules. Therefore, the use of the CA125-CAMOv2 combination could not increase the sensitivity achievable by using each respective simultaneous immunoradiometric assay.

Involucrin expression in skin appendage tumours.

The expression of involucrin was examined in 23 skin tumours of hair follicle origin, 17 tumours of sweat gland origin and three tumours of unknown origin, using an immunoperoxidase technique. All tumours from the hair follicle showed a positive reaction for involucrin. In particular keratoacanthoma and the squamous eddies in various tumours stained strongly. Trichofolliculoma, trichilemmoma and pilomatrixoma exhibited characteristic staining patterns which resembled those in the normal hair follicle. On the other hand the majority of the tumours of sweat gland origin did not stain, with restricted positive reactions in areas showing lumen formation or squamous metaplasia. In contrast to the lack of staining in syringoma, a positive reaction was observed in desmoplastic trichoepithelioma, which is histologically similar to syringoma. Clear cell acanthoma, the origin of which is still controversial, showed a staining pattern which indicated that its origin may not be in the sweat gland. These results suggest that testing for involucrin in skin appendage tumours may be very useful for understanding the kinetics of maturation as well as in determining the origin of the tumours.

Clinical evaluation of steroid receptors in ovarian neoplasms.

Estrogen and progesterone receptors were estimated in a total of 25 ovarian neoplasms. None of the benign tumors showed steroid receptors. In malignant tumors serous tumors were more often receptor positive than the mucinous. Receptor levels were correlated with the staging of the disease, menstrual status and the resectability of the tumor. The response to chemotherapeutic drugs was better in patients with low estrogen and progesterone receptors as compared to those with high levels. The latter group showed a definite response to progesterone treatment in vitro. These are the group of patients who may benefit by combination of hormones and chemotherapeutic drugs.

In vivo chemosensitivity testing in patients with gynecologic malignancies and nude mouse xenografts by monitoring cell kinetic parameters and DNA distribution patterns: a preliminary report.

Using flow cytometry (FCM) and autoradiography we have evaluated changes in DNA-ploidy patterns as well as cell-cycle perturbations after chemotherapy in 12 patients with accessible tumors and 22 nude mice xenografts. Gynecologic malignancies growing as nude mouse xenografts serve as an experimental model to study the effect of chemotherapy at the cellular level. Excellent correlation was found between fine needle aspiration (FNA) and biopsy material for either FCM or autoradiography. It now appears possible to study the effects of chemotherapy in the patient as well as the animal model using serial FNAs as a microsampling technique.

[Pathological and endocrinological study of epithelial ovarian tumors in post-menopausal women].

We have studied 37 cases of ovarian epithelial tumors in post-menopausal women, histopathologically and endocrinologically. The normal values for androstenedione, estrone, estradiol and progesterone in healthy post-menopausal women were less than 83 ng/dl, 75 pg/ml, 30 pg/ml and 0.6 ng/ml, respectively. The numbers of cases, the serum values for which were higher than normal, were 9 of 16 (androstenedione), 9 of 16 (estrone), 22 of 29 (estradiol) and 14 of 20 (progesterone). The serum levels of these 4 sex hormones in cases with ovarian stromal condensation (stromal cell hyperplasia) were higher than normal in 8 of 11 (androstenedione), 8 of 11 (estrone), 17 of 19 (estradiol) and 9 of 12 (progesterone), whereas those in cases with no stromal condensation were elevated in 1 of 5, 1 of 5, 5 of 8 and 5 of 7, respectively. After complete removal of the tumors, these elevated sex hormone levels dropped to normal. After the dexamethasone suppression test, the suppression rates for cortisol, 17-OHCS and 17-KS were 4 times as great as those of DHEA-S (dehydroepiandrosterone-sulfate), estrone, estradiol and progesterone. 17 beta-estradiol was localized in hyperplastic ovarian stromal cells in all cases with stromal condensation. We concluded that many of the ovarian epithelial tumors produce these sex hormones and that hyperplastic stromal cells are the source an increased amount of serum estradiol.

Papillary adenoma of type 2 pneumocytes.

A case of papillary adenoma of type 2 pneumocytes is reported. A 57-year-old man had an unusual coin lesion in the periphery of the right lung without any symptoms. When detected in a mass survey examination, it was approximately 1.5 cm in diameter, well circumscribed, and located in S4, involving the sixth-order bronchus of B4. Light-microscopic examination revealed cuboidal tumor cells arranged in a papillary pattern. Ultrastructurally, the cells had characteristic osmiophilic lamellar bodies. By immunoperoxidase staining, the tumor cells were shown to have intracytoplasmic surfactant apoproteins. The postoperative course was uneventful, and there is no evidence of disease 8 years later.