P53 AND KI-67 IMMUNOREACTIVITY AND NUCLEAR MORPHOMETRY OF CARCINOMA-IN-ADENOMA AND ADENOMA OF THE GALLBLADDER

Twenty intramucosal tumors of 'carcinoma-in-adenoma' and 43 adenomas ( 39 pyloric gland type, 4 intestinal type) of the gall-bladder were stu died to establish more precise histological criteria of carcinoma or a denoma in cases of 'carcinoma in pyloric gland type adenoma', to compa re carcinoma in adenoma with pure, that is, without adenomatous compon ents, carcinoma, and to confirm the benign nature of spindle cell foci in the adenomas. Ki-67 and p53 immunostaining and nuclear morphometry were used. Eight pure intramucosal cancers were used as controls. The formalin-fixed, paraffin-embedded sections were stained with p53 and Ki-67 antibodies. Spindle cell foci were observed only in the adenoma area of the pyloric gland type, with a frequency of 23% in 39 adenomas , and of 45% in 20 tumors of carcinoma-in-adenoma. Ki-67 staining was negative in 129 of 130 spindle cell foci examined, regardless of their size, and positive in only one focus (550 mu m in size, Ki-67 index 0 .2%). All of the spindle cell foci were negative for p53 stain. The Ki -67 positive index was 36.6 +/- 5.6% in the 8 pure carcinomas, and 12. 5+/-1.9% in the carcinoma area of 16 tumors with carcinoma-in-adenoma, while it was 7.9 +/- 1.7% and in the adenoma areas of 16 tumors with carcinoma-in-adenoma and 4.9 +/- 0.5% in the 32 pure pyloric gland ade nomas. The p53-protein overexpression was found in seven of eight pure intramucosal cancers, and in one of 16 cancer components of carcinoma -in-adenoma. However, it was not found in any of 16 adenoma components of carcinoma-in-adenoma, and 35 adenomas. Cells of the cancer tissue of carcinoma-in-adenoma showed a significantly larger nuclear area and a larger nuclear minor axis than those of the pyloric gland type aden omas, as well as other architectural and cytologic abnormalities diffe ring from the features of adenomas. These results suggest that cluster ed spindle cells do not indicate a malignant transformation of adenoma cells and that carcinomas In carcinoma-in-adenoma are different from pyloric gland type adenomas in terms of morphology and proliferative a ctivity. Moreover, the results of the present study indicate that carc inomas in carcinoma-in-adenoma are lower in malignancy than pure carci nomas, and that their genetic abnormality may differ from that of pure carcinomas.