Microsatellite instability is rare in rectal carcinomas and signifies hereditary cancer

Nilbert, Mef; Planck, Maria; Fernebro, Eva; Borg, Åke; Johnson, Anna

doi:10.1016/s0959-8049(99)00045-3

Cited by 64 publications

(47 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The distribution of MSI tumors varies within the colon, with about 30% of MSI tumors in the proximal colon compared to about 5% in the distal colon. 2,3,11 Our findings of loss of MLH1 in 3% and loss of MSH2 in Ͻ1% of tumors confirm these observations and suggest that other mechanisms than defective MMR cause the vast majority of rectal cancers.…”

Section: Discussionsupporting

confidence: 82%

Immunohistochemical patterns in rectal cancer: Application of tissue microarray with prognostic correlations

Fernebro

Bendahl²,

Dictor³

et al. 2004

Intl Journal of Cancer

View full text Add to dashboard Cite

We utilized the high-throughput tissue microarray method to characterize immunohistochemical expression patterns with correlations to prognosis in rectal cancer. Immunostaining for the markers Ki-67, Bcl-2, p53, EGFR, Ecadherin, ␤-catenin, MLH1 and MSH2 was performed in 269 rectal cancers. Expression profiles were correlated to metastasis-free survival. Colorectal cancer is estimated to be the second leading cause of cancer death worldwide. 1 Differences in etiology, clinical behavior, pathologic features and genetic alterations apply to right-sided vs. left-sided colorectal tumors, which indicate that different mechanisms drive tumorigenesis at these sites. 2,3 Approximately 35% of colorectal cancers are located in the rectum, and rectal cancer affects males at a rate of 1.5:1 compared to females, with 75% of cases diagnosed after 65 years of age. Treatment advances such as the standardized surgical technique TME, preoperative radiotherapy and adjuvant chemotherapy have reduced the previously high local recurrence rate and improved survival in rectal cancer patients. Despite these advances, about 40% of patients still die from disseminated disease. 4 -6 Hence, there is a need for novel markers that allow improved identification of high-risk patients who would benefit from adjuvant treatment. 7 Colorectal cancer is one of the best-characterized tumor types at the molecular level. Numerous genetic alterations in oncogenes, tumor-suppressor genes and DNA MMR genes are acquired during tumorigenesis, which occurs through successive waves of clonal expansion according to 2 major mutational pathways, the CIN and MSI pathways. 8,9 Although the sequential accumulation of genetic changes that characterize the adenoma-carcinoma sequence of colorectal cancer applies also to rectal cancer, few studies have separately analyzed these tumor types. Rectal cancer has been associated with high proliferative activity, frequent aneuploidy and loss of heterozygosity at 17p and 18q, mutation/overexpression of p53 and consequently low frequencies of diploid tumors and MSI. 2,3,10 -12 Since the frequencies of the different genetic alterations vary according to tumor location within the bowel, studies investigating a possible prognostic role of biologic parameters should optimally analyze these tumor types separately.Several tumor-associated proteins may be relevant prognostic markers in rectal cancer. However, no single molecular marker has been demonstrated to provide consistent and independent prognostic information, and despite advances in our understanding of the pathogenesis of rectal cancer, molecular markers have not gained utility in clinical decision making. 7,13,14 The TMA technology allows high-throughput analysis of molecular markers and thereby facilitates studies of multiple markers in large tumor series. 15 Our aim was to apply TMA to investigate the expression patterns of multiple markers and their prognostic correlations in a large series of rectal cancer patients. These markers, which included Ki-67, p53, Bcl-2, EGF...

show abstract

Section: Discussionsupporting

confidence: 82%

Immunohistochemical patterns in rectal cancer: Application of tissue microarray with prognostic correlations

Fernebro

Bendahl²,

Dictor³

et al. 2004

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

Section: Rectal Cancer With Msimentioning

confidence: 99%

“…This is primarily due to the rarity of dMMR in rectal cancers, with an incidence of just 2-15% of all dMMR CRC (Ishikubo et al, 2004;Nilbert et al, 1999). Despite this, it has long been established the presence of dMMR or MSI in rectal cancer is highly predictive of Lynch syndrome (≤75% cases) (de Rosa et al, 2016;Nilbert et al, 1999). Thus, whenever a dMMR rectal cancer is identified, confirmatory genetic testing should be pursued, either through direct genetic testing of MMR genes (Beamer et al, 2012;Dineen et al, 2015;Moreira et al, 2012a) or as part of a multiplex NGS gene panel (Yurgelun et al, 2015).…”

Section: Rectal Cancer With Msimentioning

confidence: 99%

The current value of determining the mismatch repair status of colorectal cancer: A rationale for routine testing

Ryan

Sheahan

Creavin

et al. 2017

Critical Reviews in Oncology/Hematology

100

118

View full text Add to dashboard Cite

“…It has been observed that MSI is rare in rectal carcinoma (Nilbert et al, 1999), whereas the incidence of CIN is high in rectal cancer (Aaltonen et al, 1998;Fernebro et al, 2002;Frattini et al, 2004). Nevertheless, compared with colon cancer, the number of mutations detected is significantly higher in rectal cancer (Frattini et al, 2004).…”

Section: Genetic Pathwaymentioning

confidence: 99%

Colorectal cancer, one entity or three

Lai

2009

J. Zhejiang Univ. Sci. B

216

163

View full text Add to dashboard Cite

Abstract:Understanding of the mechanism of colorectal carcinogenesis has been gaining momentum for some years on account of its high incidence and impact on the lives of individuals affected. Different genetic abnormalities have been found in colorectal cancers from different sites. For example, proximal colon cancer is usually related to the nucleotide instability pathway, as microsatellite instability (MSI). However, distal colon cancer is usually associated with specific chromosomal instability (CIN). The development of cancer at the rectum, though similar to that at the colon, displays its own unique features. These differences might be partially attributed to different embryological development and physiological circumstances. Environmental factors such as diet and alcohol intake also differ in their role in the development of tumors in the three segments, proximal colon, distal colon, and rectum. "Proximal shift" of colon cancer has been known for some time, and survival rates of colorectal cancer are higher when rectal cancers are excluded, both of which emphasize the three different segments of colorectal cancer and their different properties. Meanwhile, colonic and rectal cancers are distinctive therapeutic entities. The concept of three entities of colorectal cancer may be important in designing clinical trails or therapeutic strategies. However, the dispute about the inconsistency of data concerning the site-specific mechanism of colorectal carcinoma does exist, and more evidence about molecular events of carcinogenesis and targeted therapy needs to be collected to definitely confirm the conception.

show abstract

Microsatellite instability is rare in rectal carcinomas and signifies hereditary cancer

Cited by 64 publications

References 15 publications

Immunohistochemical patterns in rectal cancer: Application of tissue microarray with prognostic correlations

Immunohistochemical patterns in rectal cancer: Application of tissue microarray with prognostic correlations

The current value of determining the mismatch repair status of colorectal cancer: A rationale for routine testing

Colorectal cancer, one entity or three

Contact Info

Product

Resources

About