Purpose: Assessment of the proliferative ability of cancer cells is necessary not only for the biologic characterization of tumors, but also for the selection of treatment and evaluation of prognosis. Recently, there have been several studies examining the proliferative activity of various malignant tumors using immunohistochemical methods. PCNA is a nuclear protein related to the cell cycle and found with high expression in proliferative tissues, including cancers. Methods: In our study, to evaluate whether PCNA expression was useful as a prognostic factor in patients with pa-pillary thyroid carcinoma, we quantitated the immunohisto-chemical expression of PCNA in the formalin-fixed paraffin embedded tissue from 55 patients with papillary thyroid car-cinoma and correlated the results with established clinico-pathologic parameters. Results: The results were as follows. 1) PCNA expression in papillary thyroid carcinoma did not correlate with the age, sex or metastatic L/N activity of the patient, nor with the size, invasion, or recurrence of the tumor. 2) There was a close relationship between the expression rate of PCNA in thyroid tumor cells and that in metastatic L/N cells (p=0.056, in p0.1). 3) The expression of PCNA in the metastatic L/N (+) group was higher than in the metastatic L/N (-) group (p=0.045). Conclusion: It is suggested that PCNA expression is not an appropriate prognostic factor in papillary thyroid carcino-ma. (Korean J Endocrine Surg 2001;1:61-66)

Advanced colorectal cancer harbors extensive intratumor heterogeneity shaped by neutral evolution; however, intratumor heterogeneity in colorectal precancerous lesions has been poorly studied. We perform multiregion whole-exome sequencing on ten early colorectal tumors, which contained adenoma and carcinoma in situ. By comparing with sequencing data from advanced colorectal tumors, we show that the early tumors accumulate a higher proportion of subclonal driver mutations than the advanced tumors, which is highlighted by subclonal mutations in KRAS and APC. We also demonstrate that variant allele frequencies of subclonal mutations tend to be higher in early tumors, suggesting that the subclonal mutations are subject to selective sweep in early tumorigenesis while neutral evolution is dominant in advanced ones. This study establishes that the evolutionary principle underlying intratumor heterogeneity shifts from Darwinian to neutral evolution during colorectal tumor progression.

No abstract

Human intestinal spirochetosis is a common condition in Western countries, but is not well recognized in Japan. To demonstrate the incidence and clinicopathologic findings of human intestinal spirochetosis in Japan, we retrospectively investigated biopsy, and endoscopically or surgically resected specimens of the large intestine. Among a series of 2556 samples, 11 cases of human intestinal spirochetosis were detected (0.4%). Together with additional nine cases sporadically found, 20 cases of human intestinal spirochetosis were subjected to molecular detection of two strains of spirochetes (Brachyspira aalborgi and Brachyspira pilosicoli) by amplifying species-specific portion of 16S ribosomal RNA and NADH oxydase gene by polymerase chain reaction. B. aalborgi was detected in all cases examined, three of which revealed dual infection of both species. Our results suggest that human intestinal spirochetosis infection is relatively rare, and B. aalborgi is the most prevalent species in Japan. Most of human intestinal spirochetosis were asymptomatic, although symptomatic in exceptional cases. In addition, we emphasize a usefulness of immunostaining with anti-Treponema pallidum and anti-Mycobacterium bovis polyclonal antibodies for detecting the spirochetes.

We investigated the expression of CD10 by an immunohistochemical method in 51 basal cell carcinomas (BCCs), eight pilomatricomas, five trichoblastomas, two trichofolliculomas, three sebaceomas, five sebaceous carcinomas, ten syringomas, two spiradenomas, ten poromas, four porocarcinomas, one eccrine duct carcinoma (not otherwise specified, NOS), six mixed tumors of apocrine origin, and nine squamous cell carcinomas (SCCs). We detected strong expression of CD10 in tumor cells of BCC (86%), and found that the smaller the number of positive tumor cells, the larger the number of positive stromal cells, in particular in sclerosing BCCs. Spearman's rank correlation test revealed a significant negative correlation in BCCs between the expression of CD10 in tumor cells and that in stromal cells (P = 0.001). In all pilomatricomas (100%) and in four trichoblastomas (80%), strong expression was also detected in tumor cells. There was no detectable expression in trichofolliculomas. One sebaceoma (33%) and two sebaceous carcinomas (40%) expressed CD10 in a similar fashion to BCCs. All tumors of eccrine gland origin, including syringoma, spiradenoma, poroma, porocarcinoma, and eccrine duct carcinoma (NOS), did not express CD10. Five mixed tumors (83%) were immunopositive. In SCC, CD10 was overexpressed only in the stromal cells. These findings support the hypothesis that BCC is derived from the folliculo-sebaceous apocrine unit, especially having the same origin as trichoblastoma and pilomatricoma. CD10 might be an indicator of tumor invasiveness if it is expressed in stromal cells, while it might be a marker of follicular differentiation if it is expressed in the actual tumor cells of cutaneous epithelial neoplasms.