TY - JOUR
T1 - Differential expression of hMLH1 in sporadic human colorectal cancer tumors and distant metastases
AU - Larsen, Nicolai Balle
AU - Heiberg Engel, Peter Johan
AU - Rasmussen, Merete
AU - Rasmussen, Lene Juel
N1 - Keywords: Adaptor Proteins, Signal Transducing; Adenocarcinoma; Adenosine Triphosphatases; Adult; Aged; Aged, 80 and over; Colorectal Neoplasms; DNA Repair Enzymes; DNA-Binding Proteins; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Kaplan-Meiers Estimate; Liver Neoplasms; Middle Aged; MutS Homolog 2 Protein; Nuclear Proteins; Retrospective Studies
PY - 2009
Y1 - 2009
N2 - Somatic defects in the mismatch repair system constitute an important pathway in colorectal carcinogenesis. We have examined the expression of mismatch repair proteins in sporadic stage IV colorectal tumors and their derived metastases. Sporadic tumors were further examined for differences in expression between the tumor transition zone and the invasive front. Expression of hMSH2, hMLH1, and hPMS2 was screened immunohistochemically in 92 stage IV tumors and derived liver metastases. In cases with loss of mismatch repair protein expression, lymph node metastases were also examined. Clinicopathological parameters and Ki-67 staining indexes were evaluated and compared. Four tumors displayed a complete loss of hMLH1/hPMS2 expression at the transition zone; however, three of these expressed both proteins at the invasive front and in liver and lymph node metastases. A further four were predominantly hMLH1/hPMS2 negative at the transition zone, but with distinct subclones of hMLH1/hPMS2-expressing cells at the transition zone. All of these tumors expressed hMLH1/hPMS2 at the invasive front and in liver metastases, with three also expressing hMLH/hPMS2 in lymph node metastases. No significant difference in the proliferative index was observed for the hMLH1/hPMS2-compromised group. In stage IV tumors re-expression of hMLH1/hPMS2 occurred, leading to different patterns of expression within the primary tumor and between tumor and metastases. This may have functional importance for the chemosensitivity of metastases compared to the primary tumor.
AB - Somatic defects in the mismatch repair system constitute an important pathway in colorectal carcinogenesis. We have examined the expression of mismatch repair proteins in sporadic stage IV colorectal tumors and their derived metastases. Sporadic tumors were further examined for differences in expression between the tumor transition zone and the invasive front. Expression of hMSH2, hMLH1, and hPMS2 was screened immunohistochemically in 92 stage IV tumors and derived liver metastases. In cases with loss of mismatch repair protein expression, lymph node metastases were also examined. Clinicopathological parameters and Ki-67 staining indexes were evaluated and compared. Four tumors displayed a complete loss of hMLH1/hPMS2 expression at the transition zone; however, three of these expressed both proteins at the invasive front and in liver and lymph node metastases. A further four were predominantly hMLH1/hPMS2 negative at the transition zone, but with distinct subclones of hMLH1/hPMS2-expressing cells at the transition zone. All of these tumors expressed hMLH1/hPMS2 at the invasive front and in liver metastases, with three also expressing hMLH/hPMS2 in lymph node metastases. No significant difference in the proliferative index was observed for the hMLH1/hPMS2-compromised group. In stage IV tumors re-expression of hMLH1/hPMS2 occurred, leading to different patterns of expression within the primary tumor and between tumor and metastases. This may have functional importance for the chemosensitivity of metastases compared to the primary tumor.
U2 - 10.1111/j.1600-0463.2009.02543.x
DO - 10.1111/j.1600-0463.2009.02543.x
M3 - Journal article
C2 - 19845535
SN - 0903-4641
VL - 117
SP - 839
EP - 848
JO - Acta Pathologica Microbiologica et Immunologica Scandinavica
JF - Acta Pathologica Microbiologica et Immunologica Scandinavica
IS - 11
ER -
