Immunohistochemical Test for MLH1 and MSH2 Expression Predicts Clinical Outcome in Stage II and III Colorectal Cancer Patients

Lanza, Giovanni; Gafà, Roberta; Santini, Alessandra; Maestri, Iva; Guerzoni, Laura; Cavazzini, Luigi

doi:10.1200/jco.2005.03.2433

Cited by 192 publications

(134 citation statements)

References 58 publications

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“…Our finding of improved survival associated with MSI in colorectal carcinomas of any histologic subtype is consistent with previous reports [11][12][13]. This supports the recent WHO recommendation to grade mucinous carcinoma according to their MSI status [3].…”

Section: Discussionsupporting

confidence: 92%

“…Up to 15% of all colorectal carcinomas demonstrate MSI, more frequently secondary to acquired methylation of MLH1 (sporadic cases) than caused by a germline mutation in an MMR gene (Lynch syndrome). MSI has been reported to be a strong positive prognostic factor by multiple independent studies [11][12][13]. Some histologic subtypes of colorectal carcinomas are more commonly observed in MSI tumors, including medullary carcinomas, mucinous adenocarcinomas and signet ring cell carcinomas [14].…”

Section: Introductionmentioning

confidence: 99%

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Should the grading of colorectal adenocarcinoma include microsatellite instability status?

et al. 2014

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Adenocarcinomas of the colon and rectum are graded using a two-tiered system into histologic low-grade and high-grade tumors based on the proportion of gland formation. The current grading system does not apply to subtypes of carcinomas associated with a high frequency of microsatellite instability (MSI), such as mucinous and medullary carcinomas.We investigated the combined effect of histologic grade and MSI status on survival for 738 patients with colorectal carcinoma (48% female; mean age at diagnosis 68.2 years). The proportion of high-grade adenocarcinoma was 18%. MSI was observed in 59 adenocarcinomas (9%), with higher frequency in high-grade tumors compared with lowgrade tumors (20% vs. 6%; P<0.001). Using Cox regression models, adjusting for sex, age at diagnosis and stratifying by the American Joint Committee on Cancer (AJCC) stage, microsatellite stable (MSS) high-grade tumors were associated with increased hazard of allcause and colorectal cancer-specific mortality: hazard ratio (HR) 2.09 (95% confidence interval (CI), 1.58-2.77) and 2.54 (95% CI, 1.86-3.47), respectively, both P<0.001. A new grading system separating adenocarcinoma into low-grade (all histologic low-grade and MSI high-grade) and high-grade (MSS histologic high-grade) gave a lower Akaike information criterion value when compared with the current grading system and, thus, represented a better model fit to stratify patients according to survival. We found that patients with a high-grade adenocarcinoma had significantly shorter survival than patients with low-grade adenocarcinoma only if the tumor was MSS, suggesting that the grading of colorectal adenocarcinoma with high-grade histologic features should be made according to the MSI status of the tumor.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Should the grading of colorectal adenocarcinoma include microsatellite instability status?

et al. 2014

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“…Microsatellite instability (MSI) of more than 40% frequently occurs in right-sided colonic cancer and carries better prognostic outcomes compared to microsatellite stable (MSS) tumors [11,26]. MA of the colon might have MSI, which would affect cancer recurrence and survival [26].…”

Section: Discussionmentioning

confidence: 99%

“…High microsatellite instability (MSI-H) in CRC has been linked to higher disease-free periods and overall survival (OS); therefore, adjuvant chemotherapy is not recommended for Stage II colonic adenocarcinoma with MSI-H [11]. Furthermore, conflicting data exist regarding the effect of body mass index (BMI) and smoking status on recurrence-free survival (RFS) in CRC patients [12,13].…”

Section: Introductionmentioning

confidence: 99%

Factors associated with short recurrence-free survival in completely resected colon cancer

Alnimer

Ghamrawi

Aburahma

et al. 2017

Journal of Community Hospital Internal Medicine Perspectives

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Background: Several factors could affect disease recurrence in surgically resected colon cancer. While the role of certain factors such as cancer stage and grade is well established, the role of other factors (e.g., histological subtypes) is yet to be determined. Objective:Therefore, we conducted a study to evaluate the impact of several factors in recurrence-free survival (RFS) in patients who were disease free following surgical resection of the colon cancer. Design/Methods: Data were collected for patients with Stage I–III colon cancer who underwent complete surgical resection of the tumor between January 2010 and December 2015 in our institution. A total of 90 subjects met the inclusion criteria and were included in the study. The following factors were collected at the time of surgical resection of the colonic tumor: patient’s age, gender, colon cancer stage, grade and histological subtype, body mass index, hemoglobin A1c, and smoking history. Results: A total of 28 patients (31%) developed recurrence and had a mean follow-up time of 19.8 months (range: 2–54.4 months). Median RFS was 54.4 months with a 5-year RFS of 49%. Advanced colonic cancer stage and mucinous histological subtype were associated with shorter RFS with an HR of 2.37, 95% CI = 1.38–4.06, and 95% CI = 1.02–5.90, respectively. Current smokers or those who quit less than 15 years earlier tended to have worse RFS with an HR of 2.47, 95% CI = 0.98–6.27. Conclusion: Advanced colon cancer stage and mucinous histological subtype are independent risk factors for cancer recurrence and shorter RFS in completely resected colonic tumor.

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“…[6][7][8][9] On the contrary, other studies have failed to come to the same conclusion and have suggested that MSI þ tumors may even have worse outcome or that they do not bear a prognostic value. [10][11][12][13] Possibly, the most reliable data are provided from a recent pooled molecular analysis on a randomized trial in patients with mainly stage II (and a few III) CRC who received either 5-fluorouracil (5-FU) adjuvant chemotherapy or surgery alone. It was found in that analysis that only MSIÀ tumors benefit from the addition of adjuvant 5-FU, and that administration of chemotherapy in stage II MSI þ patients may even be harmful.…”

Section: Genetic Abnormalities In Crcmentioning

confidence: 99%

Pharmacogenetics and biomarkers in colorectal cancer

2009

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The prognosis of patients with colorectal cancer (CRC) is affected by various factors at the time of diagnosis, including location of the tumor, gender, age and overall performance status of the patient. Predicting response and limiting drug-induced toxicity for patients with CRC are also critical. Interpatient differences in tumor response and drug toxicity are common during chemotherapy. Genomic variability of key metabolic enzyme complexes, drug targets and drug transport molecules are important contributing factors. At present, there is inconsistent and rather low use of pharmacogenetic testing in the clinical setting because of a lack of robust evidence or of resources. Patients' selection and tailored treatments by the introduction of genetic testing will hopefully allow better response prediction and limit drug-induced toxicity leading to improved patient outcomes in the most cost-effective way. Here, we review the main genetic alterations observed in familial and sporadic CRC and their associations with the metabolism, efficacy and toxicities of drugs used in this disease.

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Immunohistochemical Test for MLH1 and MSH2 Expression Predicts Clinical Outcome in Stage II and III Colorectal Cancer Patients

Abstract: Immunohistochemical testing for MLH1/MSH2 expression provides useful prognostic information for the management of stage II and III colorectal cancer patients.

Cited by 192 publications

References 58 publications

Should the grading of colorectal adenocarcinoma include microsatellite instability status?

Should the grading of colorectal adenocarcinoma include microsatellite instability status?

Factors associated with short recurrence-free survival in completely resected colon cancer

Pharmacogenetics and biomarkers in colorectal cancer

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