C-ERBB-2 ONCOPROTEIN OVEREXPRESSION IN UTERINE CERVIX CARCINOMA WITH GLANDULAR DIFFERENTIATION - A FREQUENT EVENT BUT NOT AN INDEPENDENT PROGNOSTIC MARKER BECAUSE IT OCCURS LATE IN THE DISEASE

The c-erbB-2 proto-oncogene (HER-2/neu) codes for a transmembrane, tyr osine kinase, 185 kD oncoprotein (p185(erbB2)), which is related to th e epidermal growth factor receptor, p185(erbB2) overexpression occurs in carcinomas at many sites, including the uterine cervix, and predict s poor clinical outcome. The authors hypothesize that p185(erbB2) immu nohistochemistry will provide additional information in the evaluation of uterine cervix carcinomas with glandular differentiation (CCGD), a difficult and more frequent clinical problem. Paraffin sections from 82 CCGDs including 41 pure adenocarcinomas and 41 adenosquamous carcin omas (7 glassy cell predominant and 34 exhibiting a gland forming comp onent) are immunostained with anti-p185(erbB2) (CB11 monoclonal, Novac astra Laboratories, Newcastle upon Tyne, UK). Seventy-seven percent of CCGDs exhibit p185(erbB2) immunoreactivity with distinct plasma membr ane localization (M) in 50%, the remaining 27% show cytoplasmic staini ng only, Adjacent benign tissue is negative. The p185(erbB2) Staining intensity and distribution is as follows: 54.9% strong diffuse (SD, gr eater than or equal to 50% cells positive) with 40.2% M, 17.1% strong focal (SF, <50% cells positive) with 9.8% M, and 4.9% weak with no M. Immunoreactivity occurs in both squamous and glandular areas of adenos quamous carcinomas. Endometrioid histology is associated with absence of p185(erbB2) (P <.01); all other histopathologic features show no as sociation, Follow-up information is available in 77 patients: 37 exhib it recurrent disease (8 pelvic, 15 distant and 14 both) at 1 to 144 mo nths (mean 34, median 16) and 40 were disease free at 12 to 216 months (mean 75, median 64). Strong p185(erbB2) immunoreactivity predicts re currence at 23 months (P <.05) but not overall recurrence at longer fo llow-up periods. Recurrent disease is associated with nuclear grade (P <.00001); high clinical stage (P <.001); vascular space invasion (P < .001); large size on clinical exam or pathologic evaluation (P <.005); and pelvic lymph node involvement (P <.05). Considering only patients in good prognosis groups, p185(erbB2) immunoreactivity does not predi ct recurrence. Strong p185(erbB2) immunoreactivity is associated with stage 3,4 disease (P <.01). p185(erbB2) expression is associated with CCGD carcinogenesis but occurs late in the disease, in patients who pr esent at late stage, hindering its prognostic predictive value. p185(e rbB2) immunolocalization may have a diagnostic role in confirming CCGD in histologically challenging cases, predicting high stage at initial biopsy, and defining therapeutic strategies.