Increased expression of S100A6 (Calcyclin), a calcium-binding protein of the S100 family, in human colorectal adenocarcinomas.

The expression of S100A6 (also known as Calcyclin/2A9/ 5B10/PRA) in surgically resected human colorectal adenocarcinomas was examined to investigate whether S100A6 plays a role in the malignancy of human tumor cells. Western blot analysis using the lysates from colorectal adenocarcinomas and adjacent normal mucosa from 10 patients revealed that the average S100A6 level of adenocarcinomas was significantly higher (about 2.4-fold) than that of normal mucosa. Immunohistochemical analysis using formalin-fixed paraffin-embedded surgical specimens and monoclonal anti-S100A6 antibody (mAbA6) demonstrated that 2(5%) of 42 normal mucosa and 6 (46%) of 13 adenoma specimens were mAbA6-positive and showed granular staining localized at the supranuclear regions of epithelial cells, whereas 23 (55%) of 42 adenocarcinomas and 13 (100%) of 13 carcinoma cells that metastasized to the liver were mAbA6-positive and showed diffuse cytoplasmic staining. A significant correlation between S100A6 expression and Dukes' tumor stage or lymphatic permeation but not with other clinicopathological factors was shown. S100A6 was stained more intensely in peripheral portions than in central portions of adenocarcinomas, whereas Ki-67 (a growth marker) was stained equally in these two portions. These results suggest that S100A6 may be involved in the progression and invasive process of human colorectal adenocarcinomas.

Increased expression of S100A6 at the invading fronts of the primary lesion and liver metastasis in patients with colorectal adenocarcinoma.

Two members of the S100 gene family, S100A6 and S100A4 have been suggested to be associated with cancer invasion and metastasis. To study their involvement in the malignancy of human colorectal adenocarcinoma, we examined the protein expression levels of S100A6 and S100A4 in the primary colorectal adenocarcinoma (T) and paired adjacent normal colorectal mucosa (N) from 12 cases, quantitatively by Western blot analysis. In 11 of 12 and seven of 12 cases, S100A6 and S100A4 expression levels were higher in T than in N, respectively. Average S100A6 level in T was significantly higher than in N (about x 2.3;P = 0.001), whereas average S100A4 level in T was not. When S100A6 expression levels in three sets of matched samples of primary colorectal adenocarcinoma (T) and liver metastasis (M) were examined, S100A6 levels were higher in M than in T in two of three cases. Immunohistochemical analysis using monoclonal anti-S100A6 antibody showed that 23 of 42 (55%) primary colorectal adenocarcinoma and 15 of 16 (94%) liver metastasis specimens were positively stained. S100A6 immunostaining of primary colorectal adenocarcinomas was significantly more intense in the invading fronts with structural atypia than in central portions with glandular structure (P< 0.0001), whereas Ki-67 staining (a growth marker) was similar in these two portions. Interestingly, S100A6 and Ki-67 immunostaining patterns in liver metastases were also the same as in primary lesions. These results suggest that S100A6 is involved in the invasive process of human colorectal adenocarcinomas and that S100A6 expression levels decrease when carcinoma cells form glandular structure again at the central portions of metastatic nodules.