Colorectal cancer prognosis

Popat S, Hubner R, Houlston RS. Systematic review of microsatellite instability and colorectal cancer prognosis. J. Clin. Oncol. 2005 23 609-18. 

Stage of colorectal cancer should be determined at diagnosis to predict prognosis and to develop treatment options. Stage is based on the size of the primary tumor (T ), presence and extent of lymph node involvement (N0-2) and presence or absence of distant metastases (M). 

Popat, S., Matakidou, A., and Houlston, R. S. (2004) Thymidylate synthase expression and prognosis in colorectal cancer a systematic review and meta-analysis. J. Clin. Oncol. 22, 529-536. 

The clinical implications of both amplification and loss in tumors have been studied. In a study of 29 Dukes C colorectal cancer patients, those with tumors that had two or more chromosomal regions of gain or loss had significantly better prognosis than patients with less (p = 0.02) (21). Loss of chromosome 5q and lack of 8q amplification in serous ovarian cancer n = 96) is associated with improved prognosis (5-year survival of 75% versus 0% with no loss on 5q and amplification on 8q p = 0.0007) (22). In childhood ALL the amplification of specific chromosomes, chromosome regions, and genes has been associated with chemotherapy resistance and clinical outcome (23,24). 

Colorectal cancer (CRC) is the third most common cause of cancer-related death in women and men in the United States (4). Although surgical resection is the primary therapy for CRC, prognosis remains poor and not all patients are candidates for surgery. The current therapeutic options for patients with metastatic CRC (mCRC) are 5-fluorouracil (5-FU) based therapy regimens in combination with irinotecan (CPT-11) or oxaliplatin (5,6). 

Stephens RW, Nielsen HJ, Christensen IJ, Thorlacius-Ussing O, Sorensen S, Dano K, et al. Plasma urokinase receptor levels in patients with colorectal cancer Relationship to prognosis. JNatl Cancer Inst 1999 91(10) 869—874. 

Yonenaga Y, Mori A, Onodera H, Yasuda S, Oe H, Fujimoto A, et al. Absence of smooth muscle actin-positive pericyte coverage of tumor vessels correlates with hematogenous metastasis and prognosis of colorectal cancer patients. Oncology 2005 69 159-166. 

Bprresen-Dale, A.-L., Lothe, R., Meling, G., Hainaut, P., Rognum, T., and Skovlund, E. (1997) TP53 and long-term prognosis in colorectal cancer mutations in the L3 Zn-binding domain predict poor survival. Clin. Cancer Res. 4,203-210. 

Monoclonal antibodies to mutated p53 proteins have been developed. The wild type of p53 is normally present in very small amounts that are not detected by immunohisto-chemistry, whereas the mutant protein accumulates to easily detectable levels. Overexpression of the mutant proteins has been detected in up to 70% of primary colorectal cancers. Overexpression of p53 in breast cancers is associated with poor prognosis, but this association is not as strong as the association with c-erhB-2. Up to 75% of small cell lung carcinomas appear to overexpress a mutant (missense mutation) protein. Finally, circulating antibodies to mutant p53 proteins have been found in sera from patients with breast and lung cancer and B-cell lymphomas. Tills antibody response may be useful in this subset of patients for monitoring for relapse. ... 

Similarly, tumors that overexpress mutant p53 demonstrate a high degree of resistance to radiation, fluorouracil, and certain other chemotherapeutic agents and are associated with a poorer prognosis. In contrast, colorectal cancers that demonstrate low frequency microsatellite instability or microsatellite stability appear to be... 

The tumors may arise sporadically or in patients with the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome.Current experience is too limited to determine their biologic behavior and prognosis however, in one study, the patients were found to have an improved survival rate relative to those with DAs. ° Immunohistochemically, the epithelioid cells are labeled by antibodies to cytokeratins whereas trypsin, chymotrypsin, lipase, chromogranin, and synaptophysin are usually negative. CD3 antibody highlights the presence of numerous intratumoral T lymphocytes. Rare examples also contain Epstein-Barr virus RNA. ... 

Pellegrini et al. (P2) reported that combining serum TIMP-1 levels with CEA measurements in patients with colorectal cancer was useful to predict prognosis. TIMP-1 levels have been reported to be more than 3-fold elevated in patients with Dukes D (stage IV) colorectal cancer as compared to healthy donors (H7). Similar increased levels of plasma TIMP-1 were found in patients with advanced breast cancer. Holten-Andersen et al. (H7) proposed that plasma measurements of TIMP-1 may be of value in the management of cancer patients. Yukawa et al. (Y9) further reported that the plasma concentration of TIMP-1 was increased in colorectal cancer patients with serosal invasion by tumor and metastasis to lymph node and liver. 

The majority of previous immunohistochemical studies on the lymph node micrometastasis of gastric and colorectal cancers have only discussed the relationship between the presence or absence of micrometastasis and the prognosis. However, in their comparative study of lymph node micrometastasis between 10 recurrent and 9 nonrecurrent colorectal cancer cases in the pNO stage, Sasaki et al. revealed that the greater the numbers of lymph node metastases and the more distant the lymph node metastases, the higher the recurrence rate, and they proposed the introduction of a concept of... 

Y2. Yasuda, K., Adachi, Y., Shiraishi, N., Yamaguchi, K., Hirabayashi, Y., and Kitano, S., Pattern of lymph node micrometastasis and prognosis of patients with colorectal cancer. Ann. Surg. Oncol. 8, 300-304 (2001). 

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