c-erbB-2 protein expression was investigated immunohistochemically in frozen thyroid tissue specimens from 42 patients using a polyclonal sheep antibody. c-erbB-2 immunoreactivity was detected in 12 out of 17 papillary carcinomas, while no c-erbB-2 protein immunostaining was seen in cases of follicular adenoma (five cases), follicular carcinoma (five cases) or medullary carcinoma (one case), nor in cases of non-neoplastic tissue, including normal thyroid tissue from tumour-bearing glands. RNA was extracted from 51 thyroid tissue samples from 34 of the above patients, and c-erbB-2 mRNA was analysed by slot-blot hybridisation. c-erbB-2 mRNA was detectable in all samples, but papillary carcinomas and lymph node metastases showed significantly higher levels of c-erbB-2 mRNA compared to non-neoplastic tissue. The present demonstration of positive c-erbB-2 immunostaining in papillary thyroid carcinomas is contradictory to previous findings on formalin-fixed, paraffin-embedded material, and emphasises the importance of tissue quality for c-erbB-2 protein detection. Images Figure 1 Figure 3

Summary The receptor-type oncogenes c-erbB2/neu and c-erbB have been found amplified and/or overexpressed in a number of tumours of epithelial origin. We have studied the expression of oncogenes in biopsies from human thyroid tumours. The c-erbB2/neu and c-erbB oncogenes showed two-to three-fold higher levels of RNA in papillary carcinomas and lymph node metastases as well as in one adenoma when compared to non-tumour tissue. The nuclear oncogenes c-myc and c-fos were found to be expressed at varying levels in both non-tumour and tumour tissue. RNA transcripts specific for the platelet-derived growth factor A and B chains and the N-ras oncogene were detected in one anaplastic carcinoma. Neither rearrangements nor amplifications of oncogenes were observed in the thyroid tumours. These data are particularly interesting in light of the recent findings that epidermal growth factor induces proliferation and dedifferentiation of normal thyroid epithelial cells in vitro. We suggest that the epidermal growth factor or other ligands for the c-erbB and c-erbB2/neu receptors may contribute to the development and/or maintenance of the malignant phentotype of papillary carcinomas of the thyroid.

Summary In this study of papillary thyroid carcinomas, immunopositivity for EGF-receptor was present in a majority of the cases (96%), although different staining patterns were observed. A distinct membraneous reaction was found in 46%, whereas cytoplasmatic positivity of various degrees was present in 90% of the cases. Strong cytoplasmic EGF-receptor staining was significantly associated with extra-thyroidal growth of the primary tumour (P = 0.009), and it was furthermore related to decreased recurrence free survival (P = 0.006). Membraneous EGF-receptor staining was not associated with recurrence free survival or patient survival. Multivariate Cox analysis showed that lymph node metastases (P = 0.0009) and cytoplasmic EGFreceptor staining (P = 0.0048) was independent indicators of tumour recurrences in this group of surgically treated papillary thyroid carcinomas.The prognosis of patients with papillary thyroid carcinoma has previously been described in several reports (Byar et al., 1979; Tubiana et al., 1985;Carcangiu et al., 1985;Akslen et al., 1991), and the influence of sex, age and tumour stage has been discussed. In addition, certain pathological features such as marked nuclear atypia, necrosis or vascular invasion are also important (Tennvall et al., 1985;Schindler et al., 1991;Akslen et al., 1993). This information may improve the risk estimation for individual patients.In recent years, alterations in various growth factors and their receptors have been established as important features of the neoplastic process (Wynford-Thomas, 1991), among them epidermal growth factor (EGF) and its receptor (EGF-R). EGF is known to induce cell proliferation in several tissues, and its effect is mediated via a tyrosine kinase type of receptor (Carpenter & Cohen, 1979). It has previously been shown by different methods that EGF-receptors are expressed in papillary thyroid carcinomas (Duh et al., 1985;Lemoine et al., 1991;Mizukami et al., 1991; Mizukami et al., 1992), but the biological significance of this finding in terms of patient prognosis is not known. The purpose of the present study was therefore to perform a retrospective immunohistochemical study of EGF-R expression in a series of papillary thyroid carcinomas with special reference to its prognostic importance. Material and methodsPatients This material has been described previously . Briefly, all 263 patients who were surgically treated for thyroid cancer at the Department of Surgery, Haukeland Hospital, University of Bergen in the period 1971-1985 have been studied retrospectively. After histological revision and subtyping of the carcinomas according to the WHO criteria (Hedinger, 1988), 173 cases were found to be papillary carcinomas with a known primary tumour. One of the main results from our previous study was that very few events were observed in tumours with a diameter of 10 mm or below (microcarcinomas according to the WHO criteria). These were therefore excluded, thereby concentrating on clinically significant papillary carcinomas. Sufficient materia...

The findings on routine pre-operative palpation of the axilla in patients with infiltrative breast carcinoma are compared to the results of histological quantitation of the nodal lymphoid tissue and its tumour deposits in 91 consecutive cases in which a standardized axillary dissection had been carried out. The study demonstrates that lymphoid tissue, even when present in large amounts (up to 6 cm2 on histology), is seldom palpable. What the clinician identifies in favourable cases is the tumour deposit itself. When little lymphoid tissue is present very small tumour deposits (0.2 cm2) may be found on palpation, but large deposits (1 cm2) may be missed when surrounded by sufficient lymphoid tissue. These findings go far to explain the well documented unreliability of the nodal findings on axillary palpation in breast cancer.

Cortisol producing adrenal tumors ≥ 5 cm in diameter are at risk to be misdiagnosed as apparently benign. Regular surveillance should be considered in patients presenting with large cortisol producing tumors.