Distribution of collagens in carcinomas of salivary and mammary gland origin in irradiated rats

OBJECTIVE: While radiation-induced sarcomas or carcinomas following chemical carcinogens are well-documented in rats, radiation-induced carcinomas, especially adenoid-cystic carcinomas (ACC) and adenocarcinomas, originating from the head and neck region, including the major salivary glands (SG) are rarely reported. Because in human ACC of the SG structural changes of the basement membrane (BM) with positive correlation of tumor differentiation loss and BM thinning have been described, this study set out to analyze collagen distribution in malignant rat tumors (TM) developing inside the radiation field (RF) and spontaneously. The TM arose in the course of studies on other questions regarding radiation effects following fractionated radiation (2 Gy/day, 5 times a week; total dose 60 Gy).

METHODS: We investigated 22 TM (14 malignant, 8 benign) of 22 female Wistar rats. The RF comprised the left head and neck area. Besides assessment of hematoxylin-eosin (HE)-stained sections collagens (C; types III and IV) were investigated using immunohistochemical methods.

RESULTS: Nine malignant TM originated from the SG, a further three from the milk line and two from the maxilla. 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 (glandular subtype), C III was detected in the interstitium with sometimes stronger staining surrounding myoepithelial cells (MC) and excretory duct structures (ECD). Weak C IV staining in a string-like fashion was found in ECD and MC. In larger pseudocysts the lumen contained substances reacting with C IV antibodies. In the cystadenocarcinomas and the microcystic adenocarcinomas reactions at variable levels after anti-C III incubation were found close to modified MC and ECD with transition to the interstitium. C IV was more intensely stained in these entities, in part continuously and with broadening around MC and ECD. However, especially in more anaplastic parts of the tumor, fragments, interruptions or loss of the BM were noted. Focal interstitial immunoreactivity, e.g. conglomerates, was also identified.

CONCLUSION: In rat carcinomas collagen detection was partially of a continuous layer, even with BM thickening and more extended deposition. In contrast, BM fragmentation or loss was displayed more often in anaplastic parts of the tumor. Also, the interstitium showed conglomerated collagen formations. Therefore, the increasing loss of BM in rat SG tumors is similar to that in humans and in both species is a sign of dedifferentiation.