Prognostic Significance of 18q Loss of Heterzygosity in Microsatellite-Stable Colorectal Cancer
Authors: Toshiaki Watanabe, Takashi Kobunai, Yoko Yamamoto, Tsuyoshi Konishi, Hideaki Yano, Hisae Iinuma, Tamuro Hayama, Keijiro Nozawa, Soichiro Ishihara, Keiji Matsuda
Journal: Journal of Clinical Oncology (2010)

We read with interest the recent study by Ogino et al 1 on the prognostic value of the loss of heterozygosity (LOH) at chromosome 18q on survival for patients with colorectal cancer.As they introduced our study in their report, we have previously demonstrated that 18q LOH is a prognostic factor of survival in patients with colorectal cancer. 2However, in Ogino et al's study, they showed no significant difference in 5-year colorectal cancerspecific survival or 5-year overall survival between patients with 18q LOH-positive tumors and 18q LOH-negative tumors.Furthermore, multivariate analysis did not show prognostic significance of 18q LOH.From these results they concluded that 18q LOH did not associate with patient survival in patients with non-microsatellite-high colorectal cancer.However, we are concerned about the conclusion reached by the authors.There are two major issues that need to be discussed.The most important issue is the small number of stage III and high-risk stage II patients in Ogino et al's 1 study.They examined a total of 555 patients with non-microsatellite-high colorectal cancer in two independent prospective cohort studies.However, these cohorts included stage I, II, III, and IV patients.4][5] To date, many studies have been conducted in a search for a prognostic marker of colorectal cancer, and most of these studies examined stage III patients.With regard to 18q LOH, our study studies demonstrated that 18q LOH is a prognostic marker in patients with stage III and high-risk stage II colorectal cancer. 27][8] These studies focused on stage III or high-risk stage II patients because it is very important to select good candidates for intensive adjuvant chemotherapy or close follow-up after surgery in the clinical practice.In contrast, the 5-year survival rates of patients with stage I (93.2%) and stage II (82.5%) colorectal cancer are considerably high compared with that of stage III patients (59.5%). 3The 5-year survival rate of stage IV patients is only 8.1%. 3 Therefore, there is less need to establish a prognostic marker in these patients.Based on these facts, prognostic marker analysis should be performed in patients with stage III or stage III plus high-risk stage II colorectal cancer.However, in Ogino et al's study, only 163 patients (30.3% of total patients) were stage III and only 13 patients were high-risk stage II (2.3% of total patients)-almost 70% of patients were stage I, low-risk stage II, or stage IV.Another important issue is adjuvant chemotherapy.It is well known that adjuvant chemotherapy improves survival in patients with colon cancer. 9Furthermore, our previous study showed that 18q LOH status is a significant prognostic factor for patients with colorectal cancer who received fluorouracil-based adjuvant chemotherapy.In Ogino et al's 1 study, they did not show the exact number patients who had or had not received adjuvant chemotherapy.Furthermore, they did not examine the effect of adjuvant chemotherapy on survival in multivariate analysis.They need to examine the effect of adjuvant chemotherapy both in survival and multivariate analysis.Until these issues are sufficiently addressed, we believe it is premature and potentially irresponsible to conclude that 18q LOH is not associated with survival in patients with non-microsatellitehigh colorectal cancer.