Early occurrence and prognostic significance of p53 alteration in primary carcinoma of the fallopian tube.

The pathogenesis of primary carcinoma of the fallopian tube (PCFT) is poorly understood. Tumor suppressor p53 gene alterations are common in human malignancies, but their role in the tumorigenesis and survival of PCFT is undefined. The objectives of this study were to define the occurrence and prognostic role of p53 alteration in PCFT and to examine the efficiency of immunohistochemistry (IHC) in detecting p53 alteration in PCFT. Fifty-two PCFT and 10 normal fallopian tubes were examined for p53 alteration by IHC and polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP). The Kaplan-Meier method was used to derive the survival function, while the log-rank test was used to compare curves for two or more groups. Other patients' characteristics were analyzed by two-tailed Fisher's exact tests. IHC correlated well with PCR-SSCP with 100% sensitivity and 83.3% specificity for detecting p53 alteration in this study. Thirty-one of 52 (57%) PCFT showed p53 alteration. Alteration of p53 occurred in all stages of PCFT with a similar incidence in carcinoma in situ and late-stage disease. Alteration of p53 was related to tumor histologic type. Significant survival difference was noted between advanced and early clinical stages but no such difference was identified among different tumor grades. Compared to the p53-nonaltered group, the presence of p53 alteration in PCFT was related to significantly decreased patient survival (RR = 6.8, 95% CI = 2.9-16.2) in multivariate analysis. In the subgroup of patients with residual tumor after surgery, those with p53-altered tumors had a significantly decreased survival compared to those with p53-nonaltered group (RR = 7.4, 95% CI = 1.9-28.2). Alteration of p53 is common and IHC is an efficient method to detect p53 alteration in PCFT. Shorter survival is associated with p53 alteration which is an independent marker for the disease in this study. Alteration of p53 may be an early event in tubal tumorigenesis and may play an important role in the development of PCFT. Whether detection of p53 alteration may serve as an indicator of high-risk patients for whom more aggressive adjuvant chemotherapy may be considered needs to be explored in the future.

p53 overexpression and bcl-2 persistence in endometrial carcinoma: comparison of papillary serous and endometrioid subtypes.

Forty-two cases, including 21 uterine papillary serous carcinomas (UPSC) and 21 age-, nuclear-grade-, and clinical-stage-matched uterine endometrioid carcinomas (UEC), were studied immunohistochemically for p53 and bcl-2 in archival paraffin-embedded tissue. Compared to UEC (28.6% positive), UPSC (71.4% positive) had a significantly higher frequency of p53 overexpression (P = 0.005); furthermore, in a clinical-stage-matched fashion, a higher frequency of p53 overexpression was found in early-stage cases (P = 0.032), but not in late-stage cases. In a nuclear-grade-matched comparison, no statistical difference in p53 overexpression was identified between the two subtypes, although UPSC had stronger p53 immunoreactivity than UEC. Of UPSC, no difference in p53 overexpression was detected between tumors of early and late stages; additionally, in 5 cases, there was an abrupt transition from nonstaining morphologically benign glands to uniformly positive p53 nuclear staining in regions of intraepithelial carcinoma. Conversely, in UEC, there was a significant difference in p53 immunostaining between tumors of early and late stages (P = 0.01); no case had an abrupt transition for p53 immunostaining. For bcl-2 immunostaining, UEC had a significantly higher immunohistochemical staining score than did UPSC (P = 0.0002). In general, the staining intensity of bcl-2 diminished progressively from proliferative phase and hyperplastic endometrium to UEC and then to UPSC, with 3 of 21 (14.3%) UPSC being negative. These results suggest that p53 alteration may be an early event in the development of UPSC and may be related to its clinical aggressiveness, while it is a late event in UEC. Early detection of p53 nuclear accumulation may help to identify precursor lesions of UPSC. bcl-2 persistence is frequently associated with endometrial carcinoma, and failure to inactivate bcl-2 expression probably is related to the development of endometrial carcinoma.

Borderline papillary serous tumour of the fallopian tube.

We report a case of borderline papillary serous tumor of the fallopian tube in a 31-year-old woman. The tumor was characterized by the formation of papillary projections with focally prominent epithelial stratification and atypia. The histologic features of the tumor were largely similar to a borderline serous tumor of the ovary. Two years after initial presentation, the patient underwent in vitro fertilization and carried the ensuing pregnancy to term. There is no evidence of disease nearly 6 years after presentation, which suggests that these extremely uncommon tumors can be managed conservatively.

Follicle-stimulating hormone receptor is expressed in human ovarian surface epithelium and fallopian tube.

The cellular expression of pituitary gonadotropin receptors in gonadal tissues is poorly defined because of the lack of suitable reagents. In this study, we developed in situ hybridization and reverse transcription polymerase chain reaction techniques for the evaluation of follicle-stimulating hormone receptor (FSHR) expression in the ovary and fallopian tube. Using a single-strand RNA probe, we demonstrated that FSHR mRNA expression is strongest in Graafian follicles. Within these developing follicles, granulosa cells showed the greatest expression, although both theca interna and theca externa were also positive, interna greater than externa. Granulosa cells in both primary and primordial follicles were positive, with primordial follicles showing only weak focal positivity. Ovarian surface epithelium and fallopian tube epithelium, not previously recognized to express FSHR, were both strongly positive. The FSHR expression in the ovary and fallopian tube was confirmed by reverse transcription polymerase chain reaction. Our results indicated that the FSHR is expressed in a cell-specific fashion at different stages of follicular development and is also expressed in ovarian surface and fallopian tube epithelia. The presence of FSHR in ovarian surface epithelium and of gonadotropin-binding sites in ovarian neoplasms provide additional evidence supporting the derivation of epithelial ovarian tumors from the surface epithelium and should promote heightened interest in the gonadotropin theory of ovarian tumorigenesis. More importantly, this study shows the feasibility of evaluating FSHR expression by both in situ hybridization and reverse transcription polymerase chain reaction. Application of these techniques to tumor specimens will help to elucidate the role of gonadotropins and their receptors in the carcinogenesis of gynecological tumors.

Carcinomas of Bartholin's gland. Histogenesis and the etiological role of human papillomavirus.

In this study, we examine 10 primary carcinomas of Bartholin's gland, including seven squamous carcinomas, two adenoid cystic carcinomas, and one adenocarcinoma, as well as four non-neoplastic Bartholin's gland. Six of seven squamous cell carcinomas contained human papillomavirus (HPV) type 16 DNA detectable by the polymerase chain reaction; one of these demonstrated HPV type 16 by in situ hybridization. The two adenoid cystic carcinomas, the adenocarcinoma, and the non-neoplastic Bartholin's gland epithelium showed no evidence of HPV DNA by polymerase chain reaction or in situ hybridization. A panel of eight antibodies (Cam 5.2, B72.3, CEA, EMA, MCA, Lewis X, ER, and PR) demonstrate that the squamous, transition zone, duct, acinar, and myoepithelial cells or Bartholin's gland are antigenically distinct, and are similar to those reported in analogous areas of the uterine cervix. Squamous carcinoma and adenocarcinomas of Bartholin's gland are antigenically similar, and seem to arise from the transition zone of the Bartholin's gland duct. The origin of adenoid cystic carcinomas is more difficult to determine; it is distinct from squamous and adenocarcinomas and seems more likely to arise from myoepithelial cells. We conclude that adenocarcinoma and squamous cell carcinoma of Bartholin's gland arise in the transition zone of Bartholin's gland, which is similar to the transition zone of the uterine cervix. We also show that HPV is associated with Bartholin's gland carcinoma and may play a role in the genesis of malignancy.

Cytoferrin, maternofetal iron transport, and neonatal hemochromatosis.

The serum concentration of cytoferrin, a low-molecular-weight iron-binding compound, in an infant with neonatal hemochromatosis was significantly elevated (270X) by comparison with normal adult values. Concentrations of cytoferrin in cord sera from 25 normal term neonates were substantially lower but also were elevated (2X) by comparison with normal adult values. Concentrations of cytoferrin in placental tissues were comparable to values previously obtained for various mammalian tissues, and concentrations of cytoferrin in maternal sera were not elevated. This transplacental gradient in serum concentrations of cytoferrin suggests that cytoferrin may be involved in maternofetal iron transport. Although iron is known to be taken up by the hemochorial placenta via trophoblast brush border receptors for transferrin, further iron handling within the placenta is poorly understood. In particular, the routes or carriers by which iron enters the fetal circulation have not been identified. Cytoferrin may participate in stages of maternofetal iron transport distal to transferrin, and further investigation of the role of cytoferrin in neonatal hemochromatosis and other disorders may be warranted.

Term interstitial pregnancy with uterine torsion: sonographic, pathologic, and clinical findings.

Interstitial pregnancy which resulted in a term, live infant was found in association with pathologic torsion of the uterus. Antenatal sonograms revealed a hypervascular area anterior to the uterus.

Malignant Mullerian mixed tumors of the uterus: a study of 21 cases.

In a study of 21 malignant Mullerian mixed tumors of the uterus seen at The New York Hospital from 1957 to 1977, we found an unexpectedly high incidence (67%) of heterologous tumors which we attribute to an assiduous search for striated cells. Four patients, all of whom had had heterologous tumors, were free of tumor 3 1/2 to 17 years after diagnosis. The tumors were confined to the corpus and exhibited no more than moderate myometrial invasion. The heterologous element was rhabdomyosarcoma in three cases and osteosarcoma in one. Fifteen cases were treated in the last decade as compared with six in the previous decade.

Recent ovulation in a postmenopausal woman.

A case of recent ovulation in a postmenopausal, chronically alcoholic woman taking conjugated estrogens is presented. Bilateral corpora lutea, Graafian follicles, numerous corpora albicantia and secretory endometrium were found. The possible role of the prolonged alcohol and conjugated estrogens intake in modulating the pituitary-gonadal axis is discussed.