Type IV Collagen Immunostaining Is a Simple, Reliable Diagnostic Tool for Distinguishing Between Adenomatous and Normal Pituitary Glands (Report)
Pituitary adenomas are the most common intrasellar neoplasm and are often surgically resected to ameliorate clinical symptoms secondary to hormone production or mass effects. However, recent advances in radiologic imaging of the sella have led to the detection of smaller, less symptomatic pituitary tumors. Although the distinction between pituitary adenomas and other sellar tumors such as craniopharyngiomas is usually straightforward, it is often challenging to determine whether a fragment of sellar tissue represents pituitary or an adenoma. Pathologists most commonly perform immunohistochemical stains to identify a monoclonal cell population overproducing one (or a few) hormones. However, unless a specific clinical manifestation exists to guide the selection, multiple hormone stains must be performed. Because not all patients have hormone-induced symptoms, and because 20% to 30% of pituitary adenomas fail to produce histologically detectable hormone (so-called null cell adenomas), this approach is unreliable and costly. (1,2) Although chromogranin A is detectable in the majority of null cell adenomas, even this protein is present in only 71% of all tumors. (3) A tumor marker that is preferentially expressed in all adenomas would simplify and economize the diagnostic process. Currently, many investigators are studying the interactions between tumor cells and their extracellular matrix. Signals from the extracellular matrix are transduced through membrane receptors and cytoplasmic intermediaries into the nucleus, where they regulate the transcription of genes involved in cell cycling and apoptosis. One such example is the contact inhibition of the growth of tissue culture cells. Many studies have demonstrated alterations in the extracellular matrix constituents, including type IV collagen, of colorectal, biliary, and breast adenocarcinomas. (4-8) Furthermore, researchers have identified in vivo differences in the expression and/or localization of laminin, fibronectin, reticulin, and type IV collagen between normal and adenomatous pituitary tissue. Several groups have used immunostaining to show that whereas normal pituitary glands have copious laminin fibers in the epithelial basement membranes and surrounding trabeculae, adenomas have sparse laminin fibers mostly adjacent to blood vessels. (6,9,10) Murray et al (11) later confirmed the differences in laminin expression and also described decreased amounts of type IV collagen and [beta]4 integrin. Therefore, we hypothesized that the patterns of immunostaining for one of the extracellular matrix components, type IV collagen, might allow differentiation between normal pituitary gland tissue and adenomas. We undertook a retrospective analysis of pituitary adenomas and normal gland specimens to assess type IV collagen immunostaining as a diagnostic tool.