FAILURE TO DETECT COLONIC MUCOSAL HYPERPROLIFERATION IN MUTATION POSITIVE MEMBERS OF A FAMILY WITH HEREDITARY NONPOLYPOSIS COLORECTAL-CANCER

Mucosal proliferation was studied in biopsies obtained from the ascend ing colon from few: mutation positive members of a hereditary non-poly posis colorectal cancer family (group I) and compared to subjects with some positive family history of colorectal cancer but lacking the cli nical and pathological features of hereditary non-polyposis colorectal cancer (group II). Labelling indices were derived through immunohisto chemical staining of the cell cycle associated nuclear proteins prolif erating cell nuclear antigen (PCNA) and Ki-67. Only perfectly longitud inally sectioned crypts were assessed and good intra- and interobserve r reproducibility was demonstrated. The labelling indices and prolifer ative compartment locations were similar in both groups. The mean Ki-6 7 derived labelling indices (group I 18.0% and group II 17.5%) were si milar to values obtained for normal subjects in other studies. PCNA de rived labelling indices (group I 58.5% and group II 57.0%) were high, but probably reflect optimization of staining through methacarn fixati on. The negative findings do not fit with most published data but crit ical appraisal of the literature indicates that they are likely to be correct.