Cytokeratin expression in carcinomas of irradiated rats

Objective: Laboratory rats can develop benign or malignant tumors (TM) spon taneously or following various carcinogenic processes, e.g. irradiation. Th e effects of irradiation vary according to the irradiation field (RF), the dosage and the strain of rat. Radiation-induced malignant TM in rats are pr edominantly sarcomas. Carcinomas, especially adenoid-cystic carcinomas (ACC ) and adenocarcinomas of the head and neck region, are rarely reported in r ats. The aim of this study was to add to the knowledge on ACC and adenocarc inomas in rats developing inside the RF and spontaneously. The TM arose in the course of studies on other questions of radiation effects following fra ctionated irradiation (2 Gy/day, 5 times a week up to a total dose of 60 Gy ). Methods: We investigated 22 TM (14 malignant, 8 benign) of 22 female Wis tar rats. Ten malignant TM developed in the RF and 4 outside of the left he ad and neck area. The RF comprised the left neck, extending from left auric le to left clavicle and included the midline organs of the neck. Besides as sessment of hematoxylin-eosin (HE)-stained sections, epithelial differentia tion was investigated using cytokeratin (CK) antibodies against CK 5/6 CK 7 , CK 8/18, CK 13/15/16, CK 17 and CK 20 and the LSAB-2 detection system. Re sults: Nine malignant TM originated from the major salivary glands (SG), a further three from the milk line and two from the maxilla. Using HE stainin g the pattern of rat malignant TM differed from that found in humans and wa s difficult to interpret. Two ACC, two cystadenocarcinomas, one microcystic adenocarcinoma and foul squamous cell carcinomas (SCC) arising from the SG (one SCC was observed in the maxilla) developed in the RF. One microcystic adenocarcinoma, one ACC and one adenocarcinoma with sebaceous differentiat ion arising from the milk line and one SCC arising from the maxilla were fo und in non-irradiated animals. As typical results, in the ACC CK 17 was dis tinctly immunoreactive in excretory duct structures (ECD). CK 5/6 and CK 13 /15/16 were marked at variable levels in myoepithelial cells (MC) and in ba sal cells of ECD. In the cystadenocarcinomas the ECD were clearly identifie d with CK 17 and CK 8/18 antibodies. MC and basal cells of ECD were positiv e for CK 5/6 and CK 13/15/16 antibodies. Conclusion: The CK expression prof ile of these these rare and aggressive TM in mts differed according to the entity and SG structure. The differentiation markers were predominantly fou nd in ECD and in modified MC. Concerning the growth pattern of the TM, the variation in size of the cysts and pseudocysts was remarkable. The unusual tumor features reduced the comparability with humans. The differentiation p attern did not differ noticeably between TM originating inside or outside t he RF. identification of CK subtypes in rat tumors facilitates their differ ential diagnosis.