Seventy specimens of normal endometrium (n = 13) and cervix (n = 12), endometrial hyperplasia (n = 4), cervical dysplasia (n = 20), endometrial (n = 11) and cervical carcinoma (n = 8) and uterine metastases of mammary carcinomas (n = 2) have been analysed for c-erB-2 expression with immunohistochemistry employing a monoclonal anti ERBB-2 antibody and Northern-blot hybridization using single stranded RNA probes. In comparison with the c-erbB-2 mRNA expression level found in normal samples, two advanced and poorly differentiated endometrial adenocarcinomas (FIGO IV) and two ductal mammary carcinomas which had metastasized to the uterus, together with three carcinomas in situ of the cervix, showed c-erbB-2 enhanced transcription level. All other endometrial samples including adenomatous hyperplasia and nine endometrial carcinomas (FIGO I), and all other lesions of squamous epithelial origin displayed transcriptional activities at or below the baseline level. Immunohistochemical study of ERBB-2 protein expression showed staining in most samples, although different in distribution and intensity. Staining of endometrial glands was seen in unevenly distributed cells or cell clusters. In contrast, for endocervical glands, labelling was observed distinctly on basally located cells (reserve cells) and at the subapical side of luminal cells. Faint labelling of the basal cell layer was also observed in squamous epithelia. It was more pronounced in severe cervical dysplasia and carcinoma in situ. In carcinomas of glandular origin, dedifferentiation was accompanied by an increase in cytoplasmic labelling, whereas the intensity of staining was not related to differentiation in squamous cell carcinomas. While data derived from Northern blots are suggestive of c-erbB-2 overexpression to indicate an advanced and dedifferentiated state of tumours of glandular origin, staining with an anti-ERBB-2 antibody occurred in both normal and atypical squamous and glandular epithelia and may indicate regular proliferation and/or differentiation-associated events.

Normal tongue and cervical mucosa, premalignant cervical and vulvar lesions, primaries and metastases of squamous cell carcinomas from the oral, laryngeal, cervical and vulvar mucosa were analyzed for c-erbB2 and c-myc transcription with northern-blots using 32P single-stranded RNA probes. Transcription of c-erbB2 and c-myc could be detected for almost all tissues including normal samples. A slightly enhanced transcription level was found in three cervical intraepithelial neoplasias of Grade III (CIN III) but in none of the malignant lesions. Increased transcription of c-myc was observed in premalignancies and malignancies. It was more frequent in oral and laryngeal squamous cell carcinomas (SCC) (8 of 9 cases) than in genital SCC (3 of 11 cases) or premalignancies (3 CIS of 14 CIN/VIN). No relationships of c-myc enhanced transcription level with tumor grading and staging were noticed. Thus, mere oncogene expression is a widespread phenomenon in tissues of different histogenesis and quantitative analysis is necessary prior to ascribe any diagnostic or prognostic relevance. Moreover, the frequency of tumors with enhanced transcription may vary for phenotypically closely related tumors of different organs.