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R I Demopoulos

Publications and source records attributed to R I Demopoulos.

At least 19 recordsLinked to original sources
PubMed1995

Cervical squamous dysplasias and carcinomas with immunodetectable p53 frequently contain HPV.

Studies using cervical carcinoma cell lines usually show mutated p53 in cases without detectable HPV, and wild-type p53 in cases with detectable HPV. These findings suggest that loss of p53 function, either by mutation or by binding to HPV E6, is required for cervical carcinogenesis. Because mutated p53 is usually detectable immunohistochemically, one would predict an inverse relationship between the presence of HPV and detectable p53. In this study we examined 88 formalin-fixed paraffin-embedded clinical specimens of cervix for the presence of HPV and p53 expression. All cases were studied for the presence of p53 using immunohistochemical methods. The antibody used was mouse monoclonal PAb1801 (Biogenex). The presence of HPV was detected by PCR. Twenty-six specimens showed foci of p53 expression (0/7 normal, 1/8 (13%) condylomas, 1/6 (17%) CIN I, 3/7 (43%) CIN II, 6/20 (30%) CIN III, 13/22 (59%) SCC, 2/5 (40%) adenosquamous carcinomas, and 0/13 adenocarcinomas). p53 expression was more frequent in SCC than with CIN (P = 0.026). HPV was present in 15 of 24 cases with detectable p53 and 22 of 48 cases without detectable p53. No correlation was seen between HPV status and detection of p53. With the exception of one case, p53 expression was seen in less than 10% of cells. p53 expression was not detected in any of the 13 adenocarcinomas examined (P = 0.0016 vs SCC). Our results show that alterations of p53 may play a role in the pathogenesis of cervical squamous carcinoma. However, p53 expression was neither sufficient nor required for cervical carcinogenesis, irrespective of HPV status.

Adenocarcinoma↗
PubMed1995

Immunohistochemical profile of ovarian inclusion cysts in patients with and without ovarian carcinoma.

The expression of cytokeratin, epithelial membrane antigen, Leu-M1, B72.3, carcinoembryonic antigen, human placental lactogen, proliferating cell nuclear antigen, p53, and ovarian carcinoma-associated antigen OC-125 was evaluated in inclusion cysts in contralateral ovaries of patients with unilateral ovarian carcinoma. The findings were compared with the findings in inclusion cysts in ovaries of patients without ovarian carcinoma. Although there was more frequent expression of tumour markers B72.3 and CEA in patients with ovarian carcinoma, these differences did not reach statistical significance.

Biomarkers, Tumor↗
PubMed1994

Increased expression of transforming growth factor beta isoforms and basic fibroblast growth factor in complex hyperplasia and adenocarcinoma of the endometrium: evidence for paracrine and autocrine action.

Endometrial carcinoma is associated with antecedent simple and complex hyperplasia, and the endometrium is a target tissue for the action of cytokines and growth factors. Transforming growth factor (TGF)-beta s are potent cellular growth and differentiation regulatory factors. Therefore, we investigated the potential role for TGF-beta s in the normal proliferative endometrium and its possible involvement in the transition to complex hyperplasia and progression to endometrial carcinoma. The angiogenic and mitogenic growth factor, basic fibroblast growth factor, was used for comparison. Differential TGF-beta isoform-specific immunoreactivity was observed in the normal endometrium, which is composed of glandular and stromal cells. There was an increase in TGF-beta 3 but not TGF-beta 1 or TGF-beta 2 in the glandular epithelium from the proliferative to the secretory phase of the menstrual cycle. Immunostaining for TGF-beta 2 was more intense in the stroma than the glands. In contrast, TGF-beta 1 and TGF-beta 3 were near equal intensity in these two endometrial compartments, TGF-beta 3 being the most intense. The glandular epithelium demonstrated a statistically significant stepwise increase in the expression of all three TGF-beta s progressing from the normal proliferative endometrium to simple hyperplasia and on to complex hyperplasia. However, the stromal cells maintained approximately the same level of immunoreactivity for TGF-beta in all these samples. In comparing proliferative endometrium with complex hyperplasia, there was a 5.1-, 3.4-, and 2.6-fold increase in immunostaining in the glands for TGF-beta 1, TGF-beta 2, and TGF-beta 3, respectively (P < or = 0.001). There was no further increase in immunoreactivity with progression from preneoplastic complex hyperplasia to carcinoma. Immunoreactive basic fibroblast growth factor was slight in normal endometrium and simple hyperplasia. There was a 4.6- and 4.2-fold increase in immunostaining observed in complex hyperplasia compared with proliferative endometrium in the glandular (P < or = 0.0054) and stromal (P < or = 0.0053) cells, respectively, with no further increase in carcinoma. By in situ hybridization, an increase in mRNA for all TGF-beta isoforms paralleled TGF-beta immunoreactivity. However, in contrast to the increased immunostaining in the glands in complex hyperplasia, there was remarkably more mRNA in the stromal cell compartment. The discordant expression of mRNA and protein was only observed in the pathological endometrium since both were more highly expressed in the stromal cells in normal proliferative endometrium.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenocarcinoma↗
PubMed1993

Proliferating cell nuclear antigen (cyclin) expression in normal and abnormal cervical squamous epithelia.

Expression of Proliferating cell nuclear antigen (PCNA) was evaluated in formalin-fixed, paraffin-embedded normal and abnormal cervical squamous epithelia using immunoperoxidase stains and PC10 monoclonal antibody to PCNA. PCNA was exclusively expressed in the parabasal and basal layers of normal ectocervix and a similar pattern was seen in nine of the 11 cases with squamous metaplasia. Examples of cervical dysplasia showed expression in higher layers of cervical epithelium, corresponding to the degree of dysplasia. Increased staining was seen in condylomas and markedly reduced staining with atrophy. The percentage of basal cells that stained increased progressively from atrophic to normal, to condylomatous, to dysplastic epithelia. Proliferative activity can be satisfactorily assessed in formalin-fixed cervical epithelia using PC10 PCNA antibody. This assessment can be of potential diagnostic use in difficult cases.

Atrophy↗
PubMed1993

Contralateral ovary in unilateral ovarian carcinoma: a search for preneoplastic lesions.

Contralateral ovaries from patients with unilateral ovarian carcinoma were examined and compared to ovaries from age-matched control patients without ovarian carcinoma. The number of inclusion cysts were increased in ovaries from patients with ovarian carcinoma compared to the controls (p < 0.01). In addition, inclusions from cases with ovarian carcinoma showed serous differentiation more frequently than the controls (p < 0.01; odds ratio = 10.0; 95% confidence interval = 1.2-78.1). An age-related increase in the number of inclusion cysts was seen in the study group but not in the control group. These findings support a role of surface inclusion cysts in the genesis of ovarian carcinoma.

Adult↗
PubMed1993

Flow cytometric DNA ploidy and quantitative histopathology in partial moles.

This study quantitates morphologic changes seen in partial moles and hydropic abortuses in an attempt to find a correlation with DNA content. Thirty-two products of conception were studied. Fifteen were diagnosed as definitive partial moles (DPM), and 17 had changes suggestive of a partial mole (SPM). We determined DNA ploidy by flow cytometry and quantitatively analyzed the following microscopic features: villous edema and sclerosis, central cistern formation, villous blood vessels, trophoblastic proliferation, and trophoblastic inclusions. No single pathologic feature significantly correlated with DNA content, even though triploid cases showed more inclusions than diploid cases (8.3 versus 7.2 on the average per ten x 100 fields). An overall diagnosis of DPM did correlate with ploidy; 12 of 18 triploid cases (67%) compared with only three of 13 diploid cases (23%) had been previously diagnosed as DPM (p < 0.05). Flow cytometric DNA ploidy estimates DNA content and cannot determine chromosomal origin. It is possible that detailed cytogenetic studies of moles compared with abortuses may show a significant correlation of the proportion of paternal chromosomes, morphologic changes, and the risk of persistent gestational trophoblastic disease.

Abortion, Incomplete↗
PubMed1992

Patterns of keratin 19 expression in normal, metaplastic, condylomatous, atrophic, dysplastic, and malignant cervical squamous epithelium.

Keratin 19 (K-19) expression has been strongly correlated with dysplasia in oral epithelium. Expression of K-19 was evaluated by immunoperoxidase staining in formalin-fixed normal ectocervical tissue, normal endocervical tissue, cervical dysplasia, squamous metaplasia, atrophic epithelium, cervical condylomas, and invasive carcinoma to determine if a correlation of K-19 expression with dysplasia was present in the cervical epithelium. Uniform expression of K-19 was seen in endocervical epithelium and in the basal layer of normal ectocervical epithelium in all areas where these epithelia were present. Cervical dysplasia without associated condylomatous changes showed increased expression of K-19 in suprabasal epithelium, corresponding to the level of immature cells. Squamous metaplasia was characterized by scattered cells with increased staining (patch-quilt pattern). There was considerable overlap in the patterns of K-19 expression in dysplastic and metaplastic epithelium. Thus K-19 staining pattern could not be used as a distinctive marker for dysplasia in the cervical epithelium. Atrophic epithelium showed a characteristic uniform but low-level expression of K-19 in suprabasal areas. This pattern may be of diagnostic use in differentiating atrophic lesions from dysplasia. Condylomas showed focal loss of K-19 in the basal layer, suggesting induction of premature differentiation in the basal layer by human papillomavirus infection. Invasive carcinomas showed variable patterns. K-19 is a marker of immature cervical squamous epithelium, with generally distinctive but sometimes overlapping patterns of expression in various diagnostic categories.

Atrophy↗
PubMed1992

Mucinous ovarian tumors with pseudomyxoma peritonei: a clinicopathological study.

Eight patients with mucinous ovarian tumors and pseudomyxoma peritonei were matched by their original ovarian tumor histology with eight tumor controls without pseudomyxoma peritonei. In each group, four tumors were benign, three were low malignant potential, and one was malignant. Cases compared with controls more frequently showed cyst rupture (3 vs. 2), periovarian adhesions (5 vs. 4), mucinous lesions of the appendix (4 vs. 0), goblet cells (8 vs. 4), and tumor necrosis (3 vs. 1). All cases displayed pseudomyxoma ovarii, which contained mucinous epithelial cells. Only one control exhibited pseudomyxoma ovarii, but it did not contain epithelial cells. In all cases, the peritoneal mucin contained epithelial cells. Two cases were noteworthy, each of which displayed a change in histology (benign to low malignant potential and benign to malignant) 6 years after the original ovarian tumor operation. One of these cases was not associated with pseudomyxoma peritonei until the first recurrence of the benign ovarian tumor. These data suggest that pseudomyxoma ovarii, with epithelial cells, may presage the development of pseudomyxoma peritonei and/or malignant recurrence.

Appendiceal Neoplasms↗
PubMed1992

Superficial nuclear enlargement without koilocytosis as an expression of human papillomavirus infection of the uterine cervix: an in situ hybridization study.

Nuclear enlargement of the superficial cervical epithelial cells in the absence of koilocytosis is frequently observed. The purpose of this study was to investigate whether this change represents human papillomavirus (HPV) infection. We reviewed 257 cervical biopsies with the diagnosis of "suggestive of condyloma," mild or moderate dysplasia, or both. Of the 257 consecutive biopsies, 23 fulfilled the two criteria: the superficial cells had a nuclear diameter of at least twice that of the basal nuclei, and complete absence of koilocytosis was seen. Parallel sections from each paraffin block were hybridized with biotinylated probes for HPV 6/11, 16/18, and 31/35/51 under high-stringency conditions. The cases that were negative at high-stringency conditions were then hybridized under low-stringency conditions with a mixture of the three HPV probes. Twelve of the 23 cases (52.17%) were positive for HPV, including one positive for HPV 16/18 in one area and for HPV 31/35/51 in another area, four positive for HPV 31/35/51, two positive for HPV 16/18, two positive for HPV 6/11, and three positive for HPV probe mixture at low-stringency conditions. The positive in situ hybridization was located predominantly in the enlarged nuclei in the superficial layers. In conclusion, HPV infection can be expressed as nuclear enlargement in the superficial layers of the cervical epithelium in the absence of koilocytosis.

Cell Nucleus↗
PubMed1992

Phenotype of villous stromal cells in placentas with cytomegalovirus, syphilis, and nonspecific villitis.

Villous stromal cells (VSC) play an important role in fetomaternal placental immune function. We studied the phenotype of VSC in infection by cytomegalovirus (CMV) and syphilis as well as nonspecific villitis and compared the findings with gestational age-matched controls. Monoclonal antibodies directed against total leukocytes, T cells, B cells, macrophages, dendritic cells, granulocytes and HLA-DR as well as polyclonal antibodies against S-100, alpha-1 antichymotrypsin, and lysozyme were used. In controls, the immunocytochemical response for each marker was either negative or weakly positive. In contrast, the VSC in CMV-infected and nonspecific villitis showed intense reactivity to various macrophage markers. In syphilis, reactivity with macrophage markers such as lysozyme and MAC387 were weaker, and reactivity to HLA-DR and S-100 was much stronger. Endothelial cells strongly expressed the monocyte/granulocyte marker CD15 in the diseased states, especially in syphilis, relative to controls. We conclude that the phenotype of VSC is altered in disease states and that the changes are dependent to some degree on the specific subset of chronic villitis.

Antibodies, Monoclonal↗
PubMed1991

Endocervical gland involvement by cervical intraepithelial neoplasia grade III. Predictive value for residual and/or recurrent disease.

The prognostic significance for residual or recurrent disease of cervical intraepithelial neoplasia Grade III in endocervical glands by cone biopsy was examined in 341 consecutive patients diagnosed from 1979 through 1983 and followed through 1988. Treatment by hysterectomy, within 8 weeks of cone biopsy, was done in 96 patients. The only variable that could predict residual disease at hysterectomy was positive margins (P = 0.059). However, both positive margins and positive glands were (independently of one another and after the effects of length of follow-up, hospital of admission, and age at time of first diagnosis were held constant) highly significant predictors of residual or recurrent disease in the 245 women who did not undergo a hysterectomy (P = 0.000 for each). The authors therefore conclude that information concerning gland involvement on cone biopsy specimens should influence patient management.

Adult↗
PubMed1990

The prognostic significance of nuclear DNA content in malignant epithelial tumors of the ovary.

Recent studies have indicated that the nuclear DNA content of certain malignant neoplasms can be used as an adjunct in predicting their biologic behavior. The DNA content of 99 ovarian carcinomas was determined by flow cytometric analysis of nuclei obtained from paraffin-embedded tissue. Of the 99 tumors, 51 were diploid and 48 showed one or more aneuploid peaks. The 5-year survival for patients with diploid tumors (50%) was significantly higher than for patients with aneuploid tumors (22%) (P less than 0.01). Other factors which significantly affected survival were clinical stage (P less than 0.001), tumor pattern grade (P less than 0.01), DNA index (P less than 0.01), the presence of ascites (P less than 0.001), peritoneal carcinomatosis (P less than 0.0001), and residual tumor at second-look laparotomy (P less than 0.05). Diameter of the primary ovarian tumor, diameter of the largest peritoneal implant before debulking, and the percent S-phase had no significant correlation with survival. Of 16 patients with aneuploid tumors who underwent second-look laparotomy, nine (56%) had residual tumor, compared to six of 22 of patients with diploid tumors (27%). Of seven patients with aneuploid tumors and a negative second-look laparotomy, four (57%) died from recurrent tumor. By comparison, of 16 patients with diploid tumors and a negative second-look laparotomy, only four (25%) died from recurrent tumor. The determination of DNA ploidy in ovarian carcinomas may be used as an adjunct in predicting tumor behavior, response to chemotherapy, and late recurrence of disease.

Adult↗
PubMed1990

Sensitivity and specificity of various morphological features of cervical condylomas. An in situ hybridization study.

Fifty-seven cervical biopsy specimens or endocervical curettings showing condyloma, changes suggestive of condyloma, or no changes of condyloma were analyzed for presence of nuclear atypia (nuclear enlargement and irregularity in superficial epithelium), presence of multinucleated cells, and presence of perinuclear cytoplasmic clearing in superficial squamous epithelium. The findings were correlated with results of in situ hybridization with biotin-labeled human papillomavirus DNA probes. Moderate nuclear atypia was significantly more specific than perinuclear cytoplasmic clearing and 100% sensitive for predicting cases positive for human papillomavirus. Of the various morphological features analyzed, perinuclear cytoplasmic clearing had the lowest specificity for predicting positive results on in situ hybridization.

Blotting, Southern↗
PubMed1989

Analysis of multiple prognostic factors in patients with stage IB cervical cancer: age as a major determinant.

To evaluate the prognostic importance of age in patients with Stage IB cervical cancer we reviewed the results of 131 patients treated between 1974 and 1985. Patients ranged in age from 25 to 87 (mean 48) and were followed for a median of 65 months. One hundred twenty-five patients had complete follow-up information for survival analysis. Patients were divided into two groups; Group A comprising 43 patients less than or equal to age 40 and Group B comprising 88 patients greater than age 40. Both Group A and Group B patients were comparable with respect to all covariables studied. The 5-year actuarial survival for the 125 patients studied was 80%, whereas that for Group A (42 patients) and Group B (83 patients) was 54% and 91%, respectively (p = .0001). The 5-year survival for 100 surgical patients was 79% and that for Group A (36 patients) and Group B (64 patients) was 53% and 90%, respectively (p = .0001). The 5-year survival for 25 patients treated with curative RT was 65% and that for Group A (six patients) and Group B (19 patients) was 42% and 90%, respectively (p = .005). Eighteen patients were treated with adjuvant RT following surgery and their 5-year survival was 69% with three out of nine Group A and nine out of nine Group B patients alive at 65 months (p = .004). In 18 patients with pelvic nodal involvement, the 5-year survival was 48% compared to 84% in patients with negative nodes (p = .007). The difference in survival at 5 years between Group A (nine patients) and Group B (nine patients) with positive nodes was 25% and 75%, respectively. Finally, there was an increase in both local and distant failure in Group A patients. Our data illustrate that age has a profound influence on survival in women with Stage IB cervical cancer independent of potentially confounding variables.

Adenocarcinoma↗
PubMed1989

Endometrioid and clear cell carcinoma of the ovary. Factors affecting survival.

Eighty-five patients, 52 with endometrioid carcinoma (EC), nine with mixed endometrioid and clear cell carcinoma (MC), and 24 with clear cell carcinoma (CC), were studied to determine if prognosis was affected by (a) mixed tumor histology, (b) grade of the endometrioid component in ECs, and MCs, (c) presence of benign or malignant squamous differentiation in ECs, (d) solid versus tubular histology in CCs, (e) endometriosis in the same ovary as the tumor or elsewhere in the pelvis, (f) tumor stage, (g) patient age, or (h) presence of a coexisting carcinoma of the endometrium. The 5 year survivals for the ECs, MCs, and CCs were 52%, 22%, and 69%, respectively, for all stages. The 5 year survivals for Stage I ECs and CCs were 82% and 93%, respectively. None of these differences were statistically significant. Higher stages of disease for all three tumor types and higher grades of the endometrioid component of the ECs and the MCs were associated with significantly decreased survival. Patients with CCs had a significantly increased incidence of pelvic endometriosis (67%) versus patients with ECs (17%) or MCs (22%) (p less than 0.001). Survival was not significantly affected by benign or malignant squamous differentiation in ECs, tubular differentiation in CCs, patient age, the presence of endometriosis, or a coexisting carcinoma of the endometrium.

Adenocarcinoma↗
PubMed1989

Immunocytochemical staining patterns of placentas associated with hydrops fetalis.

This study examined the morphology and immunocytochemical staining patterns of distribution of beta-human chorionic gonadotropin (beta-HCG), human placental lactogen (HPL), placental alkaline phosphatase (PLAP), and pregnancy-specific beta-1 glycoprotein (SP1) in 13 third-trimester placentas associated with hydrops fetalis and six normal control placentas matched for gestational age (+/- 2 weeks). Seven placentas were hydropic (540-1,080 g) and demonstrated histologic immaturity with large edematous chorionic villi showing few blood vessels, most of which contained immature hematopoietic elements. These placentas showed consistently increased staining for beta-HCG and decreased staining for PLAP when compared with control placentas, a pattern reminiscent of less mature placentas. HPL and SP1 staining were similar to those of controls. Six placentas were either sclerotic (four) or histologically unremarkable (two), and these did not differ in their immunocytochemical staining properties from control placentas. We conclude that third-trimester hydropic placentas, in addition to showing histologic immaturity, exhibit an immunocytochemical staining pattern associated with first-trimester placentas.

Chorionic Gonadotropin↗