Cytokeratin CK 7 and CK 20 Expression in Pituitary Adenomas

Abstract

The pattern of immunohistochemical expression of cytokeratins 7 (CK 7) and 20 (CK 20) is commonly used to assess possible primary sites of metastatic carcinomas. Because pituitary tumors are almost always benign, there has been little interest in their cytokeratin profile. However, we recently reported the use of CK 7/20 expression to document malignant progression and metastasis of a pituitary tumor, indicating the potential diagnostic usefulness of the CK 7/20 profile of pituitary adenomas. We analyzed CK 7/20 expression in 97 pituitary adenomas subclassified by immunohistochemical hormone expression. In about 90% of all subtypes, CK 7 was either negative or reactive in only a few scattered cells. Corticotrophs and sparsely granulated growth hormone-positive adenomas were consistently CK 20 positive (and CK 7 negative) whereas all other subtypes were almost always CK 20 negative. This CK 20-positive, CK 7-negative profile is previously described consistently only in colonic adenocarcinomas. This study documents that subtypes of pituitary adenomas have different CK 7/20 profiles. Whereas this pattern is likely to have diagnostic usefulness in only rare adenomas, the presence of a unique CK signature in corticotrophs and sparsely granulated growth hormone-positive adenomas, subtypes particularly noted for invasive and aggressive behavior, merits further investigation.

Cytokeratin CK20 is a sensitive marker for Crooke's cells and the early cytoskeletal changes associated with hypercortisolism within pituitary corticotrophs

“…Although immunoreactivity for cytokeratin filaments has been documented in Crooke's cells [3][4][5][6][7][8] and positivity for CK8 and CK18 has been reported [7,9], these cytokeratin subsets are not specific for Crooke's cells because many in diagnostic pathology, primarily in ascertaining the primary origin of many types of metastatic adenocarcinomas. In 1992, Moll et al [10] reported that the cells of the pituitary gland were negative for CK20 expression, an observation confirmed in our recent study [13]. However, we also noted that Crooke's cells in a nonneoplastic pituitary gland adjacent to an ACTH adenoma were CK20 positive.…”

“…This polypeptide was first described by Moll et al [10], who reported in 1992 that a normal pituitary gland does not express this cytokeratin subtype. We also observed that CK20 immunopositivity is not seen in normal endocrine cells of the anterior pituitary gland, but we noted that Crooke's cells in a nonneoplastic pituitary gland adjacent to an ACTH adenoma were immunopositive for CK20 [13].…”

Diabetes insipidus due to pituitary metastasis in a woman with lung adenocarcinoma: a case report

“…Cytokeratin 20 is also always negative in pituitary adenomas. But rare pituitary adenomas like corticotrophs and sparsely granulated growth hormone-positive adenomas are consistently cytokeratin 20 positive and cytokeratin 7 negative [14]. In our patient, the tumor cells were strongly positive for thyroid transcription factor-1 and cytokeratin 7, but negative for cytokeratin 20; growth hormone level was within normal limits.…”

“…However, cytokeratin 20 is negative in primary lung adenocarcinomas and positive in colon adenocarcinomas. In pituitary adenomas, the pattern of immunohistochemical expression of cytokeratin 7 and 20 was indicative of the primary tumor origin in lung adenocarcinoma [14]. In about 90% of pituitary adenomas, cytokeratin 7 is either negative or reactive in only a few scattered cells.…”

Complex Endocrinopathies in MEN-1: Diagnostic Dilemmas in Endocrine Oncology

“…It is characterized by accumulation of a homogenous, glassy or hyaline substance in the cytoplasm; the hyaline material is composed of keratin filaments and stains with antibodies to low-molecular-weight cytokeratins and more specifically with cytokeratin (CK) 20 [15]. This change results from exposure to glucocorticosteroid excess either by exogenous administration or as a result of endogenous glucocorticoid hypersecretion caused by primary adrenal disease or ectopic ACTH production [5].…”