ABSTRACT
IGF-I is one of the peptides that participates in normal adrenocortical cell growth and, possibly, in the genesis and/or maintenance of tumors and hyperplasias of the adrenal cortex. An immunohistochemical technique was used for the analysis of IGF-l expression in eight control and four hyperplastic adrenals, 11 adrenal cortical adenomas, and 18 adrenal cortical carcinomas. A large number of IGF-I positive cells with granular cytoplasmic (GC) staining pattern was found in the reticularis layer of control adrenal tissues. Fifty percent of the hyperplasias had the GC pattern and the other 50% a mixed pattern; in 64% of the tumors, the adenomas showed a LM (linear membrane) pattern, while adenocarcinomas usually showed a GC pattern (94%). Approximately 75% of the hyperplasias had between 10 and 50% of IGF-l positive cells, while adenomas and carcinomas had over 50% of IGF-I positive cells in 64% and 83% of the samples, respectively. The size of the tumors with 50% positive cells, compared with those with less than 50%, was, on average, greater, but no statistical differences between cell positivity and corresponding clinical syndrome were observed. Thus, detection of IGF-l in control and pathological adrenal tissue suggests participation of this growth factor in cell function and/or growth and proliferation.
ABSTRACT
Pituitary carcinomas are very rare neoplasms with a poor prognosis. We report a case of Cushing's disease resulting from a pituitary carcinoma in a 22-yr old female, who died of massive hepatic failure. At autopsy, there was invasion of the parasellar structures and vasculature by the tumor, which stained positively only for ACTH. There were two metastatic nodules in the liver, which also stained positively for ACTH. When compared to other cases of Cushing's disease (n = 52), other pituitary adenomas (n = 292). and normal pituitary tissues (n = 21), the pituitary carcinoma was the only one with c-erbB-2 membrane staining in both the sellar-located tissue and liver metastasis. C-erbB-2 staining 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 immunohistological 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 primary tumor and liver metastasis (10%) was also found compared to other ACTH-secreting adenomas (invasive, 3.4 -t 1 S% vs 1 ii +/- 1.5% in noninvasive) and other pituitary tumors (invasive, 2.9 +/- 1.5% vs 1.5 +/- 1.3% in noninvasive). The PCNA index was significantly higher in invasive tumors than in noninvasive adenomas (p = 0.004). PCNA staining was negative in normal pituitary tissues. Staining for p53, pRB and p(2ras) was negative in the carcinoma and liver metastasis. We suggest that the c-erbB-2 membrane pattern and a higher PCNA index may indicate a worse prognosis in adenohypophyseal neoplasia.
