Progesterone receptor immunoreactivity in pancreatic endocrine tumors. An immunocytochemical study of 156 neuroendocrine tumors of the pancreas, gastrointestinal and respiratory tracts, and skin

Abstract

Background. The immunoreactivity for progesterone receptors (PR) of the majority of endocrine cells of the human pancreas has prompted the authors to investigate if PR expression is maintained in pancreatic endocrine tumors and is correlated with the main clinicopathologic features of these neoplasms. Furthermore, the study has been extended to other neuroendocrine cells and tumors to determine whether PR immunoreactivity is a common feature of neuroendocrine cells and tumors other than those of the pancreas. Methods. One hundred fifty six neuroendocrine tumors of the pancreas, gastrointestinal and respiratory tracts, and skin were immunostained for PR with three different monoclonal antibodies and for estrogen receptors (ER). Additional immunostainings for general neuroendocrine markers and for pancreatic hormones were performed in selected cases. Results. Nuclear immunoreactivity for PR has been documented in the neoplastic cells of 56 (58.33%) of 96 pancreatic endocrine tumors. PR immunoreactivity was not influenced by the sex and age of the patients or the occurrence of a clinical syndrome related to inappropriate hormone secretion. Tumors synthesizing pancreatic polypeptide, glucagon, and insulin expressed PR in higher percentages (80%, 75%, and 6670, respectively) than those producing other pancreatic hormones or those that were not functioning. Irrespective of the functionally different tumor types, PR immunoreactivity showed a significant correlation (P = 0.0003) with the absence of metastases and the lack of tumor invasion of neighboring organs or of large vessels. As opposed to normal and neoplastic islet cells, the neuroendocrine cells and tumors of the gastrointestinal tract, respiratory tract, and skin did not show any PR immunoreactivity, with the single exception of a typical carcinoid tumor of the lung. ER were not identified in any pancreatic or extrapancreatic neuroendocrine cells or tumors. Conclusions. Nuclear PR are immunocytochemically detectable in most pancreatic endocrine tumors and are correlated significantly to the absence of pathologic evidence for malignancy. Conversely, PR expression has not been found in normal and neoplastic endocrine cells and tumors investigated. Cancer 1992; 70:2268‐2277.

Nonductal neoplasms of the pancreas

“…Normal islet cells express progesterone receptors and CD 99, and about half of PENs label for these markers as well. 9,41,42 Proliferation markers such as Ki67 are expressed in less than 10% of the neoplastic cells, and in most cases the rate is between 5% and less than 1%. 1,4,14,43 Genetic studies have identified many chromosomal alterations in PENs; however, activation of oncogenes has not been implicated in their development.…”

“…9 Nuclear pleomorphism is also not a useful predictor, 30 although some studies have demonstrated a correlation between overall nuclear grade and prognosis. 9 Other factors reportedly predictive of more aggressive behavior (at least in univariate analyses) include loss of progesterone receptor expression, 42,43 aneuploidy, 70,71 increased Ki67 labeling index, 43,72 loss of heterozygosity (LOH) of chromosome 17p13, 20 LOH of chromosome 22q, 73 increased fractional allelic loss, 74 upregulated CD44 isoform expression, 75,76 and immunohistochemical expression of cytokeratin 19. 77 A number of grading schemes have been proposed for PENs, including some that attempt to separate them into benign and malignant groups as well as others that simply stratify the risk for recurrence.…”

Nuclear Receptors and Their Selective Pharmacologic Modulators

“…Interestingly, they are also expressed in the brain, bone, pancreas, testes, and lower urinary tract (Viale et al, 1992;Clarke, 1997, 2002;Bland, 2000;Han et al, 2009;Tincello et al, 2009). Examination of the phenotype of PR-null animals has provided significant insight into the explicit functions of the two PR isoforms.…”

Expression and functional consequences of oestrogen and progesterone receptors in human insulinomas

“…There have been a limited number of studies characterising the steroid hormone receptor profile of pancreatic tumours. PRs have been detected immunohistochemically in normal pancreas and pancreatic tumours, almost exclusively being confined to endocrine pancreas tissue (Doglioni et al 1990, Viale et al 1992. A decade ago, oestrogen receptor (ER) presence was demonstrated in pancreatic tumour tissue using radioligand binding assays and Scatchard analysis (Greenway et al 1981).…”