PTEN mRNA expression is less pronounced in left- than right-sided colon cancer: a retrospective observational study.
Several recent studies have reported that patients with metastatic colorectal cancer (CRC) whose primary tumor is located in left side of the colon have more favorable responses to anti-epidermal growth factor receptor (EGFR) antibody therapy than those with right-sided tumors. However, the mechanism for this phenomenon is unknown.



Fifty-two cases of primary CRC with liver metastases were analyzed in this retrospective study. The mRNA levels of 19 signal transduction genes in both primary tumor and liver metastases were measured by real-time reverse transcription polymerase chain reaction. The purposes of this study were (1) to determine the correspondence between signal transduction gene expressions in primary tumors and corresponding liver metastases, and (2) to determine whether expression levels of these genes differ by primary tumor location.



mRNA expression levels of 14 of 19 signal transduction genes, including PTEN, ERBB2, MET, HGF, AREG, and EREG, showed significant correlations between the primary tumor and corresponding liver metastases. When the mRNA levels of the primary tumors were compared by tumor location, only PTEN mRNA expression differed significantly between left and right-sided CRC (median PTEN expression: left 1.00 vs. right 1.68; p = 0.017). When rectal cancers were separated from left-sided colon cancers, PTEN mRNA levels increased progressively from rectum to right-sided colon (median; rectum 0.84, left colon 1.23, right colon 1.68, p = 0.013). PTEN mRNA expression in liver metastases also differed significantly according to primary tumor location (median; left 0.92 vs. right 1.27, p = 0.048). There was no difference in overall survival between patients with high versus low levels of PTEN mRNA (p = 0.59).



Our data suggest that the PIK3/AKT/mTOR pathway is more active in left- than right-sided CRC, which provides a possible explanation for the fact that efficacy of anti-EGFR therapy differs by location of primary tumor.
Department of Chemotherapy and Palliative Care, Tokyo Women's Medical University, 8-1 Kawadacho, Shinjuku-ku, Tokyo, Japan. kuramochi.hidekazu@twmu.ac.jp.|Department of Surgery, Tokyo Women's Medical University, Yachiyo Medical Center, 477-96 Owadashinden, Yachiyoshi, Chiba, 276-8524, Japan. kuramochi.hidekazu@twmu.ac.jp.
Hidekazu
H
Kuramochi
Department of Chemotherapy and Palliative Care, Tokyo Women's Medical University, 8-1 Kawadacho, Shinjuku-ku, Tokyo, Japan.
Ayako
A
Nakamura
Department of Chemotherapy and Palliative Care, Tokyo Women's Medical University, 8-1 Kawadacho, Shinjuku-ku, Tokyo, Japan.
Go
G
Nakajima
Department of Gastrointestinal Surgery, Tokyo Women's Medical University, 8-1 Kawadacho, Shinjuku-ku, Tokyo, Japan.
Yuka
Y
Kaneko
Department of Surgery, Tokyo Women's Medical University, Yachiyo Medical Center, 477-96 Owadashinden, Yachiyoshi, Chiba, 276-8524, Japan.
Tatsuo
T
Araida
Department of Gastrointestinal Surgery, Tokyo Women's Medical University, 8-1 Kawadacho, Shinjuku-ku, Tokyo, Japan.
Masakazu
M
Yamamoto
Department of Chemotherapy and Palliative Care, Tokyo Women's Medical University, 8-1 Kawadacho, Shinjuku-ku, Tokyo, Japan.
Kazuhiko
K
Hayashi
D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D008297:Male; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012189:Retrospective Studies
D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D012333:RNA, Messenger; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D016283:Proto-Oncogene Proteins p21(ras)
Colorectal cancer; Gene expression; Liver metastases; PTEN; Primary tumor location; Signaling pathway