Expression of epidermal growth factor receptor and HER-2/neu in normal and neoplastic cervix, vulva, and vagina.

Monoclonal antibodies were used to localize immunohistochemically epidermal growth factor receptor and HER-2/neu in normal and neoplastic frozen tissue samples from the lower genital tract of women. In squamous epithelia of the cervix, vulva, and vagina, epidermal growth factor receptor and HER-2/neu both were expressed most strongly by basal keratinocytes. Expression of both of these cell surface molecules decreased as cells underwent differentiation toward the mucosal surface. In contrast, both epidermal growth factor receptor and HER-2/neu were expressed throughout the entire thickness of the epithelium by undifferentiated squamous cells in squamous metaplasia, raised condyloma, and carcinoma in situ. In 34 squamous cancers of the cervix, vulva, and vagina, all malignant cells were found to have moderate to heavy staining for epidermal growth factor receptor. Staining of 33 of these cancers for HER-2/neu was light, although one patient who presented with distant metastases had heavy staining for HER-2/neu. These data suggest that although overexpression of HER-2/neu in squamous cancers of the lower genital tract is a rare event, it may be associated with aggressive biologic behavior.

Human papillomavirus DNA in genital tract lesions histologically negative for condylomata. Analysis by in situ, Southern blot hybridization and the polymerase chain reaction.

Koilocytotic atypia (nuclear atypia in conjunction with perinuclear halos) is diagnostic of condylomata of the lower female genital tract, over 90% of which contain human papillomavirus (HPV) DNA. Genital tract lesions may be clinically suggestive of condylomata but lack clear-cut koilocytotic atypia. Of 57 vulvar and 60 cervical lesions that lacked clear-cut koilocytotic atypia, four (7%) and two (3%), respectively, had HPV DNA detected by in situ analysis. Using Southern blot analysis, HPV DNA was detected in five of 27 (19%) and 20 of 55 (36%) vulvar and cervical lesions, respectively, that lacked koilocytotic atypia. When analyzed with the polymerase chain reaction (PCR), HPV DNA was detected in six of 22 (27%) and three of 18 (17%) vulvar and cervical lesions, respectively, that lacked koilocytotic atypia. These findings demonstrate that infection by HPV may be found in genital tract lesions that lack koilocytotic atypia. The lower detection rate of HPV in cervical lesions that lacked koilocytotic atypia with PCR as compared with Southern blot analysis may be related to the relatively high proportion of "novel" types (related to, but distinct from, the HPV types in the probe) in such lesions. The increase in the detection rate in vulvar lesions that lacked koilocytotic atypia with PCR compared with in situ hybridization suggests that about one third of such lesions are HPV related, but that in such cases the copy number of the virus is typically below the threshold of the in situ analysis.

A nuclear deoxyribonucleic acid analysis of normal and abnormal vulvar epithelium.

Vulvar and groin skin from 21 women with clinical squamous cell carcinoma of the vulva was compared with that from nine patients with vulvar intraepithelial neoplasia. Feulgen-stained nuclear densitometry showed a constancy of Feulgen-deoxyribonucleic acid (DNA) density in normal epithelium and all subepithelial connective tissue nuclei. At three sites--tumor edge, opposite labia, and perineum--there were significant differences in nuclear chromatin content between the two groups and also as compared with normal epithelium.

Estrogen and progesterone receptor assays on the vulvar epithelium.

Seventy-seven samples of healthy and diseased vulvar epithelium (one per patient) were processed using the carbon-coated-dextran biochemical technique. The results were analyzed according to Scatchard or the unique point technique. The samples of normal tissue were obtained from patients who underwent surgical procedures for different gynecologic pathologies. The samples of diseased tissue were obtained with punch biopsy from patients with several vulvar disorders. Ten samples were obtained from the episiotomy wound in pregnant patients during labor. Estrogen receptors were assayed in all cases. Progesterone receptors were assayed simultaneously in 73 of the cases. The minimum concentration considered positive was 2 fmol/mg of protein. A map of the vulvar region was drawn, and samples were obtained from different sites whenever possible.

[Steroid hormone receptors in normal, dystrophic, dysplastic and carcinomatous vulva tissues]. / Steroidhormon-Rezeptoren in normalen, dystrophischen, dysplastischen und karzinomatösen Vulvageweben.

We employed the agar gel electrophoresis method to determine in 63 samples of vulva tissue the cytoplasmatic receptors for oestradiol, dihydrotestosterone and dexamethasone. Tissues with a binding capacity of more than 5 femtomol/mg (fmol = 10(-15) mol) cell proteins were considered receptor positive. The study comprised 17 normal tissues of the vulva, 13 vulva biopsies at the end of the pregnancy period, 7 dystrophically changed tissues, 11 premalignant changes of the vulva and 15 squamous cell carcinomas. In normal as well as in benign or malignantly changed vulva, specific receptors were found for all the four steroids (ER, PR, DHTR, DExaR). Receptors were most frequent in normal vulva tissue (ER = 94%, PR = 54%, DHTR = 38%, DexaR = 83%) with binding-capacities of 8-650 fmol/mg cell proteins. ER levels were higher during the postmenopausal period than during the premenopausal period. In dystrophia the receptor pattern was almost the same as in healthy tissue. Biopsies conducted at the end of the pregnancy period showed in all cases despite the high endogenous oestrogen levels positive ER values up to 875 fmol/mg cell proteins, whereas PR and DTHR were present in only 20% or 25% with low binding capacities. Loss of receptors, particularly of PR, was seen in premalignant changes (dysplasia of vulva, carcinoma in situ) and in case of squamous cell carcinomas. On comparing the receptor distribution of clinically changed vulva tissue with healthy tissue we found only differences by degree but no fundamental differences in principle.(ABSTRACT TRUNCATED AT 250 WORDS)

Sex steroid receptors in normal and malignant human vulvar tissue.

Receptors for estrogens, progesterone and androgens were assayed in 6 specimens of normal vulvar tissue and in 9 specimens of carcinomatous vulvar tissue. These receptors were not always present in all specimens examined. In both normal and carcinomatous tissues receptor concentration was highly variable. Malignant tissues did not show significant changes in values compared to normal tissue.