Cytokeratin expression in carcinomas of irradiated rats

OBJECTIVE: Laboratory rats can develop benign or malignant tumors (TM) spontaneously or following various carcinogenic processes, e.g. irradiation. The effects of irradiation vary according to the irradiation field (RF), the dosage and the strain of rat. Radiation-induced malignant TM in rats are predominantly sarcomas. Carcinomas, especially adenoid-cystic carcinomas (ACC) and adenocarcinomas of the head and neck region, are rarely reported in rats. The aim of this study was to add to the knowledge on ACC and adenocarcinomas in rats developing inside the RF and spontaneously. The TM arose in the course of studies on other questions of radiation effects following fractionated 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 Wistar rats. Ten malignant TM developed in the RF and 4 outside of the left head and neck area. The RF comprised the left neck, extending from left auricle to left clavicle and included the midline organs of the neck. Besides assessment of hematoxylin-eosin (HE)-stained sections, epithelial differentiation 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.

RESULTS: Nine malignant TM originated from the major salivary glands (SG), a further three from the milk line and two from the maxilla. Using HE staining the pattern of rat malignant TM differed from that found in humans and was difficult to interpret. Two ACC, two cystadenocarcinomas, one microcystic adenocarcinoma and four 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 differentiation arising from the milk line and one SCC arising from the maxilla were found in non-irradiated animals. As typical results, in the ACC CK 17 was distinctly 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 basal cells of ECD. In the cystadenocarcinomas the ECD were clearly identified with CK 17 and CK 8/18 antibodies. MC and basal cells of ECD were positive for CK 5/6 and CK 13/15/16 antibodies.

CONCLUSION: The CK expression profile of these rare and aggressive TM in rats differed according to the entity and SG structure. The differentiation markers were predominantly found 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 pattern did not differ noticeably between TM originating inside or outside the RF. Identification of CK subtypes in rat tumors facilitates their differential diagnosis.