METALLOTHIONEIN EXPRESSION IN NONMELANOMA SKIN-CANCER - AN IMMUNOHISTOCHEMICAL STUDY

Histopathologically demonstrated metallothionein (MT) overexpression h as been associated with poor clinical outcome in a variety of tumors. Using a monoclonal anti-MT antibody (E9), we investigated the profile in nonmelanoma skin cancer: 12 solar keratoses (SKs), six Bowen diseas es (BDs), 24 squamous cell carcinomas (SCCs), 10 keratoacanthomas (KAs ), 59 basal cell carcinomas (BCCs) of all types, six recurrences, and eight lymph node metastases of primary skin cancer. In normal human sk in, the epidermal basal cell layer, peripheral follicular and sebaceou s epithelia, hair matrix cells, peripheral cell layer of eccrine ducts , and myoepithelial cells are MT positive. In reactive inflammatory le sions this MT expression is more prominent, and additional structures such as nerves, smooth muscle cells, (myo)fibroblasts, dermal dendrocy tes, and pericytes are also (partially) labeled. In SK, BD, and well- to moderately differentiated SCC, only the peripheral (basal and supra basal) cell layers are (mostly) labeled for MT, whereas in all poorly differentiated SCCs (nine of 24), irregular clusters and sheets of tum or cells above the level of the peripheral cell layers show MT labelin g (MT overexpression). KAs either show labeling of the tumor periphery or, in case of regression, no or weak reactivity for MT. MT overexpre ssion similar to poorly differentiated SCC was also seen in 16 of 59 B CCs and all recurrent or secondary lesions of primary skin cancer. Dur ing a mean follow-up of 5 years, the risk of tumor recurrence and/or m etastasis was statistically significantly increased for patients with MT overexpression in the SCC (p < 0.05) and BCC (p = 0.0001) series co mpared with those patients without MT overexpression. Our findings ind icate that labeling for MT in nonmelanoma skin cancer parallels the pr ogressive potential of these lesions and thus may have some prognostic value.