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High frequency of microsatellite instability and loss of mismatch-repair protein expression in patients with double primary tumors of the endometrium and colorectum

Planck, Maria LU ; Rambech, Eva LU ; Moslein, G; Muller, W; Olsson, Håkan LU and Nilbert, Mef LU (2002) In Cancer 94(9). p.2502-2510
Abstract
BACKGROUND. Patients with the familial syndrome hereditary nonpolyposis colorectal carcinoma (HNPCC) exhibit air increased risk for several tumor types, of which the greatest lifetime risk is for colorectal and endometrial carcinoma. HNPCC is caused by a germline mutation in one of several identified mismatch repair (MMR) genes and typically presents with microsatellite instability (MSI) and frequent loss of NMR protein expression in the tumor tissue. The objective of this study was to estimate the proportion of double primary tumors of the endometrium and colorectum that displays tumor characteristics suggestive of MMR deficiency. METHODS. The authors used the southern Sweden regional population-based Cancer Registry to identify women who... (More)
BACKGROUND. Patients with the familial syndrome hereditary nonpolyposis colorectal carcinoma (HNPCC) exhibit air increased risk for several tumor types, of which the greatest lifetime risk is for colorectal and endometrial carcinoma. HNPCC is caused by a germline mutation in one of several identified mismatch repair (MMR) genes and typically presents with microsatellite instability (MSI) and frequent loss of NMR protein expression in the tumor tissue. The objective of this study was to estimate the proportion of double primary tumors of the endometrium and colorectum that displays tumor characteristics suggestive of MMR deficiency. METHODS. The authors used the southern Sweden regional population-based Cancer Registry to identify women who developed double primary tumors of tire endometrium and colorectum. Of the 256 women who were diagnosed with carcinoma at both of these sites during the period 1958-1998, 39 women had developed their first tumor before age 50 years. The authors successfully retrieved 67 tumors from 36 of these patients and analyzed them for MSI and immunohistochemical expression of the MMR genes, MLH1, MSH2, and MSH6. RESULTS. The MSI status of the 67 tumors was high MSI in 37 tumors, low MSI in 13 tumors, and microsatellite stable (MSS) in 17 tumors. Immunohistochemical loss of MMR protein expression was correlated with MSI status and was demonstrated in 29 high MSI turners, in 1 low MSI tumor, and in 1 MSS tumor. A concordant loss of the same MMR protein in both tumors was found in 12 of 27 patients. CONCLUSIONS. The authors demonstrated a high frequency of MSI (75%) in tumors from women with endometrial and colorectal carcinoma who had their first tumor diagnosed before age 50 years and observed concordant immunohistochemical loss of MMR protein expression, suggestive of a possible underlying germline mutation, in 12 of 27 patients (44%). They concluded that double primary malignancies of the colorectum and endometrium at a young age should make the clinician suspect (C) 2002 American Cancer Society. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
immunohistochemistry, mismatch-repair protein expression, instability, microsatellite, endometrial carcinoma, colorectal carcinoma, hereditary nonpolyposis colorectal carcinoma
in
Cancer
volume
94
issue
9
pages
2502 - 2510
publisher
John Wiley & Sons
external identifiers
  • wos:000175310200023
  • pmid:12015776
  • scopus:0036570140
ISSN
1097-0142
DOI
10.1002/cncr.10501
language
English
LU publication?
yes
id
bea5fd26-e78a-442a-9499-58201ad0545c (old id 339664)
date added to LUP
2007-11-09 08:01:41
date last changed
2017-01-01 04:40:43
@article{bea5fd26-e78a-442a-9499-58201ad0545c,
  abstract     = {BACKGROUND. Patients with the familial syndrome hereditary nonpolyposis colorectal carcinoma (HNPCC) exhibit air increased risk for several tumor types, of which the greatest lifetime risk is for colorectal and endometrial carcinoma. HNPCC is caused by a germline mutation in one of several identified mismatch repair (MMR) genes and typically presents with microsatellite instability (MSI) and frequent loss of NMR protein expression in the tumor tissue. The objective of this study was to estimate the proportion of double primary tumors of the endometrium and colorectum that displays tumor characteristics suggestive of MMR deficiency. METHODS. The authors used the southern Sweden regional population-based Cancer Registry to identify women who developed double primary tumors of tire endometrium and colorectum. Of the 256 women who were diagnosed with carcinoma at both of these sites during the period 1958-1998, 39 women had developed their first tumor before age 50 years. The authors successfully retrieved 67 tumors from 36 of these patients and analyzed them for MSI and immunohistochemical expression of the MMR genes, MLH1, MSH2, and MSH6. RESULTS. The MSI status of the 67 tumors was high MSI in 37 tumors, low MSI in 13 tumors, and microsatellite stable (MSS) in 17 tumors. Immunohistochemical loss of MMR protein expression was correlated with MSI status and was demonstrated in 29 high MSI turners, in 1 low MSI tumor, and in 1 MSS tumor. A concordant loss of the same MMR protein in both tumors was found in 12 of 27 patients. CONCLUSIONS. The authors demonstrated a high frequency of MSI (75%) in tumors from women with endometrial and colorectal carcinoma who had their first tumor diagnosed before age 50 years and observed concordant immunohistochemical loss of MMR protein expression, suggestive of a possible underlying germline mutation, in 12 of 27 patients (44%). They concluded that double primary malignancies of the colorectum and endometrium at a young age should make the clinician suspect (C) 2002 American Cancer Society.},
  author       = {Planck, Maria and Rambech, Eva and Moslein, G and Muller, W and Olsson, Håkan and Nilbert, Mef},
  issn         = {1097-0142},
  keyword      = {immunohistochemistry,mismatch-repair protein expression,instability,microsatellite,endometrial carcinoma,colorectal carcinoma,hereditary nonpolyposis colorectal carcinoma},
  language     = {eng},
  number       = {9},
  pages        = {2502--2510},
  publisher    = {John Wiley & Sons},
  series       = {Cancer},
  title        = {High frequency of microsatellite instability and loss of mismatch-repair protein expression in patients with double primary tumors of the endometrium and colorectum},
  url          = {http://dx.doi.org/10.1002/cncr.10501},
  volume       = {94},
  year         = {2002},
}