ADRENOCORTICOTROPIN-PRODUCING PITUITARY CARCINOMA WITH EXPRESSION OF C-ERBB-2 AND HIGH PCNA INDEX - A COMPARATIVE-STUDY WITH PITUITARY-ADENOMAS AND NORMAL PITUITARY TISSUES

Pituitary carcinomas are very rare neoplasms with a poor prognosis. We report a case of Gushing's disease resulting from a pituitary carcino ma in a ZZ-yr-old female, who died of massive hepatic failure. At auto psy, there was invasion of the parasellar structures and vasculature b y the tumor, which stained positively only for ACTH. There were two me tastatic nodules in the liver, which also stained positively for ACTH. When compared to other cases of Gushing's disease (n = 52), other pit uitary adenomas (n = 292), and normal pituitary tissues (n = 21), the pituitary carcinoma was the only one with c-erbB-2 membrane staining i n both the sellar-located tissue a nd liver metastasis. C-erbB-2 stain ing was present in the cytoplasm of a variable number of cells in 40% of the invasive adenomas (n = 103), while only 1.2% of the noninvasive tumors (n = 241) expressed this protein (p < 0.001). No particular im munohistological type preferentially expressed this protein. In normal pituitary tissues, 10% of the cells expressed cytoplasmic c-erbB-2. A higher index of proliferating cell nuclear antigen (PCNA) in the prim ary tumor and liver metastasis (10%)was also found compared to other A CTH-secreting adenomas (invasive, 3.4 +/- 1.9% vs 1.7 +/- 1.5% in noni nvasive) and other pituitary tumors (invasive, 2.9 +/- 1.5% vs 1.5 +/- 1.3% in noninvasive). The PCNA index was significantly higher in inva sive tumors than in noninvasive adenomas (p = 0.004). PCNA staining wa s negative in normal pituitary tissues. Staining for p53, pRB and p(21 ras) was negative in the carcinoma and liver metastasis. We suggest th at the c-erbB-2 membrane pattern and a higher PCNA index may indicate a worse prognosis in adenohypophyseal neoplasia.