Differential Expression of Spectrin Isoforms in Benign and Malignant Epithelial Tumors
Y Wang, J Albanese, H Ratech. Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY
Background: Spectrin is a rod-like, multifunctional molecule composed of an α-subunit and a β-subunit. There are multiple spectrin isoforms that can bind actin and associate with other proteins to help integrate structure and function in complex tissues. Because embryonic liver fodrin, a variant of β-spectrin, has recently been implicated in the pathogenesis of hepatocellular carcinoma, we hypothesized that various spectrin isoforms might be involved in other epithelial tumors. We report the first comprehensive study of the expression and localization of spectrin isoforms in normal human epithelial tissues and in their benign and malignant counterparts.
Design: We retrospectively studied the expression of spectrin isoforms αI, αII, βI, βII and βIII by immunohistochemical staining of normal epithelial tissues as well as benign and malignant neoplasms from 66 specimens involving breast, colon, kidney, liver, prostate, thyroid, uterine cervix and transitional epithelium of urinary bladder.
Results: The majority of normal epithelial cell types expressed αII spectrin. Normal uterine cervical squamous mucosa expressed αII spectrin in the basal and parabasal cells, but not in the keratinized superficial layers; the pattern for βI spectrin was the inverse for αII spectrin. For example, we found βI spectrin in the superficial, but not in the basal epithelium of the uterine cervix. Compared to their normal epithelial counterparts, there was loss of αII spectrin in papillary thyroid carcinoma, in clear cell renal carcinoma and in invasive ductal breast carcinoma. Expression of βI spectrin was limited to normal hepatocytes, transitional umbrella cells of the bladder, type II pneumocytes of the lung, mature superficial squamous epithelium of the uterine cervix, and lobular and ductal epithelium of the breast. In contrast to the absence of staining for βI spectrin in normal biliary ductules, thyroid follicles and renal tubules, we detected aberrant expression of βI spectrin in biliary ductal carcinoma, thyroid papillary carcinoma and renal clear cell carcinoma. Spectrin isoforms βII and βIII were universally present in both benign and malignant epithelial tumors.
Conclusions: Loss or gain of specific spectrin isoforms occur both during normal epithelial maturation and in some examples of neoplastic transformation. This suggests the possibility of a significant role for spectrin isoforms in carcinogenesis.
Wednesday, March 24, 2010 9:30 AM
Poster Session V # 225, Wednesday Morning