Morphological and molecular heterogeneity within nonmicrosatellite instability-high colorectal cancer

Vicki L.J. Whitehall; Coral V.A. Wynter; Michael D. Walsh; Lisa A. Simms; David Purdie; Nirmala Pandeya; Joanne Young; Stephen J. Meltzer; Barbara A. Leggett; Jeremy R. Jass

Morphological and molecular heterogeneity within nonmicrosatellite instability-high colorectal cancer

Vicki L.J. Whitehall, Coral V.A. Wynter, Michael D. Walsh, Lisa A. Simms, David Purdie, Nirmala Pandeya, Joanne Young, Stephen J. Meltzer, Barbara A. Leggett, Jeremy R. Jass

Research output: Contribution to journal › Article › peer-review

111 Scopus citations

Abstract

Colorectal cancer (CRC) has traditionally been classified into two groups: microsatellite stable/low-level instability (MSS/MSI-L) and high-level MSI (MSI-H) groups on the basis of multiple molecular and clinicopathologic criteria. Using methylated in tumor (MINT) markers 1, 2, 12, and 31, we stratified 77 primary CRCs into three groups: MINT++ (>2), MINT+ (1-2), and MINT- (0 markers methylated). The MSS/MSI-L/ MINT++ group was indistinguishable from the MSI-H/MINT++ group with respect to methylation ofp16^INK4a, p14^ARF, and RIZ1, and multiple morphological features. The only significant difference between MSI-H and non-MSI-H MINT++ cancers was the higher frequency of K-ras mutation (P < 0.004) and lower frequency of hMLH1 methylation (P < 0.001) in the latter. These data demonstrate that the separation of CRC into two nonoverlapping groups (MSI-H versus MSS/MSI-L) is a misleading oversimplification.

Original language	English (US)
Pages (from-to)	6011-6014
Number of pages	4
Journal	Cancer Research
Volume	62
Issue number	21
State	Published - 2002
Externally published	Yes

ASJC Scopus subject areas

Oncology
Cancer Research

Cite this

@article{0681871e82d247b9a3f87f972b9c9680,

title = "Morphological and molecular heterogeneity within nonmicrosatellite instability-high colorectal cancer",

abstract = "Colorectal cancer (CRC) has traditionally been classified into two groups: microsatellite stable/low-level instability (MSS/MSI-L) and high-level MSI (MSI-H) groups on the basis of multiple molecular and clinicopathologic criteria. Using methylated in tumor (MINT) markers 1, 2, 12, and 31, we stratified 77 primary CRCs into three groups: MINT++ (>2), MINT+ (1-2), and MINT- (0 markers methylated). The MSS/MSI-L/ MINT++ group was indistinguishable from the MSI-H/MINT++ group with respect to methylation ofp16INK4a, p14ARF, and RIZ1, and multiple morphological features. The only significant difference between MSI-H and non-MSI-H MINT++ cancers was the higher frequency of K-ras mutation (P < 0.004) and lower frequency of hMLH1 methylation (P < 0.001) in the latter. These data demonstrate that the separation of CRC into two nonoverlapping groups (MSI-H versus MSS/MSI-L) is a misleading oversimplification.",

author = "Whitehall, {Vicki L.J.} and Wynter, {Coral V.A.} and Walsh, {Michael D.} and Simms, {Lisa A.} and David Purdie and Nirmala Pandeya and Joanne Young and Meltzer, {Stephen J.} and Leggett, {Barbara A.} and Jass, {Jeremy R.}",

year = "2002",

language = "English (US)",

volume = "62",

pages = "6011--6014",

journal = "Cancer Research",

issn = "0008-5472",

publisher = "American Association for Cancer Research Inc.",

number = "21",

}

TY - JOUR

T1 - Morphological and molecular heterogeneity within nonmicrosatellite instability-high colorectal cancer

AU - Whitehall, Vicki L.J.

AU - Wynter, Coral V.A.

AU - Walsh, Michael D.

AU - Simms, Lisa A.

AU - Purdie, David

AU - Pandeya, Nirmala

AU - Young, Joanne

AU - Meltzer, Stephen J.

AU - Leggett, Barbara A.

AU - Jass, Jeremy R.

PY - 2002

Y1 - 2002

N2 - Colorectal cancer (CRC) has traditionally been classified into two groups: microsatellite stable/low-level instability (MSS/MSI-L) and high-level MSI (MSI-H) groups on the basis of multiple molecular and clinicopathologic criteria. Using methylated in tumor (MINT) markers 1, 2, 12, and 31, we stratified 77 primary CRCs into three groups: MINT++ (>2), MINT+ (1-2), and MINT- (0 markers methylated). The MSS/MSI-L/ MINT++ group was indistinguishable from the MSI-H/MINT++ group with respect to methylation ofp16INK4a, p14ARF, and RIZ1, and multiple morphological features. The only significant difference between MSI-H and non-MSI-H MINT++ cancers was the higher frequency of K-ras mutation (P < 0.004) and lower frequency of hMLH1 methylation (P < 0.001) in the latter. These data demonstrate that the separation of CRC into two nonoverlapping groups (MSI-H versus MSS/MSI-L) is a misleading oversimplification.

AB - Colorectal cancer (CRC) has traditionally been classified into two groups: microsatellite stable/low-level instability (MSS/MSI-L) and high-level MSI (MSI-H) groups on the basis of multiple molecular and clinicopathologic criteria. Using methylated in tumor (MINT) markers 1, 2, 12, and 31, we stratified 77 primary CRCs into three groups: MINT++ (>2), MINT+ (1-2), and MINT- (0 markers methylated). The MSS/MSI-L/ MINT++ group was indistinguishable from the MSI-H/MINT++ group with respect to methylation ofp16INK4a, p14ARF, and RIZ1, and multiple morphological features. The only significant difference between MSI-H and non-MSI-H MINT++ cancers was the higher frequency of K-ras mutation (P < 0.004) and lower frequency of hMLH1 methylation (P < 0.001) in the latter. These data demonstrate that the separation of CRC into two nonoverlapping groups (MSI-H versus MSS/MSI-L) is a misleading oversimplification.

UR - http://www.scopus.com/inward/record.url?scp=0036827692&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036827692&partnerID=8YFLogxK

M3 - Article

C2 - 12414620

AN - SCOPUS:0036827692

SN - 0008-5472

VL - 62

SP - 6011

EP - 6014

JO - Cancer Research

JF - Cancer Research

IS - 21

ER -

Morphological and molecular heterogeneity within nonmicrosatellite instability-high colorectal cancer

Abstract

ASJC Scopus subject areas

Other files and links

Fingerprint

Cite this