LSI Library




UT Southwest article regarding important information on biallelic mutations

Canadian study describes a novel biallelic condition  10/2012




  1. 7/25/2012  A study from Canada sends a strong message: . MSH2 carriers should be offered screening for cancer of the entire urothelium, as they are at an increased risk for both bladder AND upper tract cancers
  2. Risk of Urothelial Bladder Cancer In Lynch Syndrome Is Increased, In Particular, Among MSH2 Mutation Carriers JMedGenet2010  Netherlands Study, Radboud University
  3. From Pubmed:  Reviews in Urology: 2003 Winter 5(1) 49-53    Urothelial Carcinoma in a Man with Hereditary Nonpolyposis Colon Cancer, by Dean L. Lenz, MD and Lewis E. Harpster, MD, Department of Surgery, Division of Urology, Pensylvania State University, Milton S. Hershey Medical Center, Hershey, Pennsylvania. Synopsis:  HNPCC should be considered in any individual with a developed upper tract urothelial cancer or a suggestive family history.
  4. Risk for Urologic Cancer Linked to Risk for Colorectal Cancer WebMD CME Library
  5. Upper Urinary Tract  Carcinoma In Lynch Syndrome Cases - Swedish study of U.S. participants from Creighton University data.  Majority of participants had MSH-2 and sustained ureter cancer a mean 15.8 years after a primary cancer.  Median age was 62.  Equal gender ratio and high grade tumors similar to that in the geneal population.
  6. A Study From France:  21.3% Of All Upper Urinary Tract Urothelial Carcinomas May Have Underlying Lynch Syndrome As a Cause. 6/15/2012
  7. Impact of Distal Ureter Management on Oncologic Outcomes Following Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma   Collaborated letter on the gold standard for urinary tract urothelial carcinoma.  July 2012





  1. 8/21/2012  Dr. James Ford of Stanford University addresses the question, "Is Breast Cancer A Part of Lynch Syndrome?"  A "Must Read" for genetic counselors and medical professionals 
  2. Evidence of Breast Cancer As An Integral Part Of Lynch Syndrome   Swiss study of six families of hundreds of persons with 92 female mutation carriers with MLH1 and MSH2 mutations, mean age 49 to 50 years old, consistent with the mean cancer rate of the average population (56.5 years of age) MSI present in 26 of 37 (70.3%) and altered MMR expression in 16 of 22 (72.7%) Lynch syndrome carriers.  Conclusion was findings presented a strong molecular evidence for a pivotal role of MMR deficiency in breast cancer development in Lynch syndrome.  10/27/2011
  3. Lynch Syndrome-Associated Breast Cancers:  Clinicopathologic Characteristics of a Case Series from the Colon Cancer Family Registry Walsh, Buchanan, Cummings, Pearson, Arnold, Clendenning, WAlters, McKeone, Spurdle, Hopper, Jenkins, Phillips, Suthers, George, Goldblatt, Muir, Tucker, Pelzer, Gattas, Woodall, Parry, Macrae, Haile, Baron, Potter, LeMarchand, Bapat, Thibodeau, Lindor, McGuckin, Young Authors' Affiliation: Familial Cancer Laboratory, Molecular Cancer Epidemiology Laboratory, Queensland Institute of Medical Research, University of Queensland School of Medicine, University of Queensland Centre for Clinical Research, Genetic Health Queensland, Royal Brisbane and Women's Hospital, Herston, Mater Medical Research Institute, South Brisbane, Queensland, Australia; School of Population Health, Centre for MEGA Epidemiology, University of Melbourne, Melbourne, Australia; Department of Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Parkville, Victoria, Australia; South Australian Clinical Genetics Service, North Adelaide, Department of Paediatrics, University of Adelaide, South Australia, Australia; Genetic Services of Western Australia, King Edward Memorial Hospital, Subiaco, School of Paediatrics and Child Health, University of Western Australia, Nedlands, Western Australia, Australia; Clinical Genetics Service, Prince of Wales Hospital, Randwick, New South Wales, Australia; Northern Regional Genetics, Auckland Hospital, University of Auckland, Auckland, New Zealand; Keck School of Medicine, University of Southern California, Los Angeles, California; Dartmouth Medical School, Hanover, New Hampshire; Fred Hutchinson Cancer Research Center, Seattle, Washington; Cancer Research Center of Hawaii, University of Hawaii at Manoa, Honolulu, Hawaii; Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Canada; and Mayo Clinic, Rochester, Minnesota.
  4. Unusual Presentation of Lynch Syndrome London Study 2009, Male Breast Cancer
  5. Lynch Syndrome Associated Breast Cancers - Clinicopathological Characteristics Of A Case Study From The Colon Cancer Registry - David Walsh, MD, Familial Cancer Laboratory Queensland  51% of all breast cancers in individuals with Lynch syndrome indicated MMR deficiency.  Breast cancer may therefore represent a valid tissue option for the detection of MMR deficiency in which spectrum tumors are lacking.
  6. Early Onset Breast Cancer In A Lebanese Family With Lynch Syndrome Due to MSH-2 Gene Mutation, Rizk Hospital, Beirut, Lebanon 5/28/2009
  7. Lynch Syndrome- The Influence of Environmental Factors On Extracolonic Cancer Risk on hMLH1 C.c1528T Mutation Carriers and Their Mutation Negative Sisters South Africa Study - Extracolonic cancer occurred in 14 percent of the mutation carrier females. Breast cancer was the most extracolonic cancer.
  8. Colorectal And Other Cancer Risks For Carriers and Non-Carriers From Families With A DNA Mismatch Repair Gene Mutation - A Prospective Cohort Study/  An International Study That Is a Must Read Discussing the Risks of Specific Cancers of Lynch Syndrome And One Of The First Comprehensive Studies On The Risk of Breast Cancer Within Lynch Syndrome
  9. J Clin Oncol 30, 2012 (suppl 4; abstr 413) Breast Cancer In Irish Families With Lynch Syndrome Breast cancer occurred at an early age and was more common than prostate cancer in Irish Lynch Syndrome pedigrees. All reported breast cancer cases were in kindreds with MSH2 or MSH6 mutations. Enhanced breast cancer screening may be warranted in certain Lynch Syndrome kindreds.
  10. Breast Cancer and South African Females, 2010, Lynch syndrome: the influence of environmental factors on extracolonic cancer risk in hMLH1 c.C1528T mutation carriers and their mutation-negative sisters.  Breast cancer was double that of those studied without mutations.





  1. Small Bowel Adenocarcinoma Phenotyping, a Clinical Prognostic StudySuggests molecular alterations in small bowel adenocarcinomas (SBA) are closer to those in colorectal cancer (CRC) than gastric cancer, with low levels of HER 2 overexpression and high frequencies of KRAS mutations. Seemingly higher frequency of MMR deficiency (dMMR) than in CRC may be explained by higher frequency of LS in SBA patients. A dMMR phenotype was significantly associated with a non-metastatic tumour (P=0.02). A trend for a good prognosis and a duodenum or jejunum primary site was associated with dMMR.British Journal of Cancer advance online publication, 5 November 2013; doi:10.1038/bjc.2013.677
  2. 6/2012  University of Groeningen, Netherlands, discusses small bowel surveillance for Lynch syndrome.  Recent data indicates capsule endoscopy shows promising results for those with Lynch syndrome and who have a 5% lifetime risk of contracting small bowel cancer.
  3. Parent of Origin Effects On Age At Colorectal Diagnosis Large collaborated study of many institutions concluded affected daughters of affected fathers were, on average, younger than affected sons of affected mothers.  Results need confirmation in an independent study before cliinical significance can be determined.
  4. Distinct Mutations in MLH1 And MSH2 Genes in Hereditary Non-Polyposis Colorectal Cancer HNPCC Families From China
  5. 1/2011 According to Aukland, New Zealand study, individuals with more extensive colonic  resections have a lower risk of metastasized cancers than those receiving less extensive resections.
  6. DNA Repair System Affects Colon Cancer Recurrence and Survival - Mayo Clinic Study data of more than 2,000 clinical trial patients who had Stage 2 and Stage 3 cancers, and were treated with 5FU chemotherapy protocol, concluded patients with mismatched repair had lower rates of tumor recurrence, longer remissions, fewer metasteses and better survival rates compared to those without defects.
  7. 12/2010 Expeditious colonoscopy following discovery of mutation status in patients may benefit newly identified mutation carriers by addressing objective risks for cancer and alleviating underlying emotional distress responses to genetic risk information.
  8. Impact of Colonoscopy Screening On Individuals At High Risk for Hereditary Nonpolyposis Colorectal Cancer HNPCC  Spain - Conclusion, Colonoscopy is effective in detecting colorectal adenomas and cancer in individuals with HNPCC - Men have a greater number of colorectal adenomas  2011
  9. The Impact Of Colonoscopy Screening In Male And Female Lynch Syndrome Carriers With An MSH-2 Mutation A study from Newfoundland Canada  Study of repeat cancers between screening intervals. Within two years of a colonoscopy, 20% of the males and 7% of the females developed an interval of CRC.  CRC development may further be reduced by decreasing the interval to one year and improving quality of colonoscopy.
  10. Infiltration Of Lynch Colorectal Cancers By Activated Immune Cells Associates With Early Staging Of The Primary Tumor And Absence Of Lymph Node Metastases Leiden University Medical Center, 1/18/2012  Conclusion:  The immune system assumes an important role of counteracting the progression of Lynch colorectal cancers and in selecting abnormal HLA Class I phonetypes.  Findings support the development of clinical strategies that explore the hosts natural anti-tumor immune responses.
  11. Colonoscopic screening at 3-year intervals more than halves the risk of CRC, prevents CRC deaths, and decreases overall mortality by about 65% in HNPCC families.Controlled Fifteen Year Trial on Screening For Colorectal Cancers In Families With Hereditary Polyposis Colorectal Cancer. May 1, 2000  Helsinki University Central Hospital, Helsinki
  12. Colonoscopic surveillance reduces the risk of colorectal cancer in people with a strong family history. This study confirms that members of families with hereditary non-polyposis colorectal cancer require surveillance with short intervals. Prevention of Colorectal Cancer By Colonoscopic Surveillance in Individuals With A Family History of Colorectal Cancer: 16 Year Prospective Follow Up Study Family Cancer Group, Cancer Research UK Colorectal Cancer Unit, St Mark's Hospital, Harrow, Middlesex HA1 3UJ.  BMJ  11/5/2005
  13. 1/2013  Rectal Cancer and the Lynch syndrome: ...less common than colon cancer,RC is an important component of LS and may be overrepresented in MSH2 mutation carriers. Given high risk of synchronous or metachronous cancers, appropriate surveillance for second malignancies is necessary.



  1. Genetic Testing Strategies in Newly Diagnosed Endometrial Cancer Patients Aimed at Reducing Morbidity or Mortality from Lynch Syndrome In the Index Case or Her Relatives  (Allison Stewart, PhD, CDC Consultant)  9/16/2013

  2. Risk of Colorectal Cancer after Diagnosis of Endometrial Cancers:  A Population-Based Study article by Science Daily  October, 2012
  3. 7/2012  From Advances in Anatomic Pathology:  The risk of gynecologic malignancy in women with LS approaches and even exceeds that of CRC. Gynecologic malignancies are often the sentinel cancers in these patients.  Article reviews the morphologic and clinical features/schemas in LS EC and highlight limitations of restrictive aged-based screening strategies, uncertainty in current clinical schemas and equivocal results of morphologic studies of LS EC. With uncertainty of histologic and clinical schemas, and following developments in CRC, reflex testing of all/vast majority of newly diagnosed EC for LS should be considered.
  4. 8/2012  From the Archives of Gynecology and Obstetrics, study reinforces endometrial sampling is essential for women with Lynch syndrome.
  5. 8/2012  From Obstetrics and Gynecology:  Genetic Testing for Lynch Syndrome, An Inherited Cancer of the Bowel, Endometrium and Ovary  - Very nice article with good forms for taking family histories and a nice graph of a standard management plan.
  6. Molecular Analysis of endometrial pathogenesis in Lynch syndrome, J Clin Onco 29 2011, MD Anderson, Ottawa University, concluded hyperplasia is part of the pre-invasive spectrum of LS associated EC.  While PTEN loss was common in both LS and sporadic EC, PIK3CA and CTNNB1 mutations were more frequent in sporadic EC than LS EC. Our results indicate that loss of PTEN expression is an early event in sporadic EC and that other common mutations in sporadic EC may have a lesser role in LS associated EC development.
  7. Association of Lynch Syndrome and Risk of Invasive Cervical Cancer, 2010 ASCO Conference, J Clin Oncol 28:15S 2010  Conclusion:  Cervical cancer is associated with Lynch syndrome and the histology of cervical cancers in MMR mutation carriers may vary from expected population standards.
  8. Primary Peritoneal Cancer After Bilateral Salpingo-Oophorectomy in Two Patients With Lynch Syndrome. Schmeler, Kathleen M, MD, Daniels, Molly S; Soliman, Pamela T, MD MPH;  Broaddus, Russel R, MD PhD; Deavers, Michael T. MD; Vu, Thuy M. MS; Chang, George J. MD, MS; Lu, Karen H. MD
  9. Endometrial Cancer and Lynch Syndrome, Moffit Hospital, MD Anderson
  10. Risk Reducing Surgery in Women At Hereditary Risk of Gynaecological Cancer Czech study, 6/2011  Risk reducing Salpingo Oopherectomy or Hysterectomy is the most effective strategy for gynecological cancer prevention in susceptability gene mutation carriers so far.
  11. Risk of Endometrial Cancer For Women Diagnosed With HNPCC Related Colorectal Carcinoma - Conclusion:  One quarter of women diagnosed with Lynch Syndrome associated CRC developed EC within ten years.  University of Queensland 12/1/2010
  12. Testing Women With Endometrial Cancer To Detect Lynch Syndrome, University of British Columbia 6/2011  Women may not be identified by Amsterdam 2 criteria.  IHC triage at any age, having at least 1 FDR, with a Lynch associated cancer, is a cost effective strategy for detecting Lynch syndrome.
  13. US/Canadian study recommends reflex testing for all endometrial cancers. 7/2012
  14. Researchers Propose Screening For Lynch Syndrome In All Patients With Newly Developed Endometrial Cancer 4/2011
  15. Hysteroscopy In Diagnosing Lynch Syndrome  Endometrial Cancer Screening In Patients With Lynch Syndrome  J Clin Oncol 29: 2011 (suppl; abstr 5108)
  16. Association of Lynch Syndrome and Invasive Cervical Cancer  J Clin Oncol 28:15s, 2010 (suppl; abstr 1501)




  1. 7/6/2012  Newfoundland study indicates gynecological screening did not result in earlier gynecologic cancer detection and despite screening two young women died from ovarian cancer suggesting that prophylactic hysterectomy with bilateral salpingo-oophorectomy be considered in female mutation carriers who have completed childbearing.
  2. A Swedish and Danish study indicated ovarian cancer with Lynch syndrome presents at young age with early non-serous tumors indicating a family history of colorectal and endometrial cancers should be specifically considered in such cases.
  3. Ovarian Cancer Linked To Lynch Syndrome Typically Presents as Early Onset Non-Serous Epithelial Tumors  Gynecol Oncol. 2011 Jun 1;121(3):462-5. Epub 2011 Mar 9.
  4. Endometrial and Ovarian Cancer Screening and Prevention In Women With Lynch Syndrome 
  5. 11/31/2012  Prevalence of loss of expression of DNA mismatch repair proteins in primary epithelial ovarian tumors  Study demonstrated the loss of MMR protein expression in 10.1% of endometriosis-associated ovarian carcinomas. 




  1. Risk of Pancreatic Cancer In Lynch Syndrome Families 2009, JAMA  Dana Farber, Michigan State, Conclusion:  The risk of pancreatic cancer is eight times higher than the risk of the general population
  2. Lynch Syndrome Tied to Breast and Pancreatic Cancer 2/21/2012
  3. Hereditary, Pancreatic and Hepatobiliary Cancers  International Journal of Oncology 2011  Paper discussing the risk and studies regarding pancreatic cancer and Lynch syndrome




  1. From the American Journal of Medical Genetics, Part A, Vol 121A Issue 2, Pgs 159-162, pub 3/26/2003, European researchers publish case study of prostate cancer in Lynch syndrome.
  2. Prostate Cancer Found In Lynch Syndrome Patient
  3. Neuendocrine type prostatic adenocarcinoma with microsatellite instability in a patient with Lynch syndrome December of 2010, University of Nebraska Medical Center, Findings suggested HGPIN-NE is a percursor of invasive SCC and also that prostatic SCC can develop in a patient with Lynch syndrome.
  4. Hereditary Prostate Cancer As A Feature of Lynch Syndrome U. Of Mich, Ann Arbor, 3/2011  35 tumors underwent MSI Analysis, 2 of which were MSI high and 1 of which was MSI-low. Conclusion: PCa may arise in Lynch syndrome due to defective DNA mismatch repair.
  5. Hereditary, Pancreatic and Hepatobiliary cancers  - International Journal of Oncology, 2011  Paper discussing risk and studies regarding pancreatic cancer and Lynch syndrome.

  6. Manchester UK study discovers a ten fold risk of prostate cancer has been determined with MSH2.  Other significant findings are also noted.  

  7. Ohio State Study: Prostate cancer incidence was not increased in this relatively large cohort of LS patients.




  1. 8/6/2012  Dr. Maxwell Fung, University of California - Davis, discusses IHC - MSI testing of tumors for Muir Torre  
  2. 2012 Article, University of California-Davis, Mt. Sinai Dermatology Online  Muir Torre - Turcot Syndrome overlap?
  3. 8/2012  MSH-6 Family Detected With Muir Torre
  4. 7/2012  Mismatch Repair Protein Deficiency Is Common In Sebaceous Tumor Neoplasms
  5. 7/2012  Polypoid Adenoid Carcinoma Detected in the Efferent Jejunal Loop following gastrectomy in a Muir Torre Patient.  
  6. Acute Myloid Leukaemia Associated With Muir Torre Variant Of Hereditary Non Polyposis Colon Cancer (HNPCC) "Implications for inherited and acquired mutations in DNA mismatch repair genes  9/13/2011 British Journal of Haematology , Volume 156, Issue 2, January 2012
  7. Glastiobloma Multiforme In the Muir Torre syndrome: From Johns Hopkins
  8. A New Mutation In Muir Torre Associated With Familiar Transmission Of Different Gastrointestinal Adenocarinomas - Hungary
  9. The Frequency of Muir-Torre Syndrome Among Lynch Syndrome Families: Christopher D. South , Heather Hampel , Ilene Comeras , Judith A. Westman , Wendy L. Frankel , Albert de la Chapelle, JNCI Journal of the National Cancer Institute Advance Access published February 12, 2008  
  10. Italian Researchers have discovered prevelance of Muir Torre associated with the liver in a Lynch syndrome family.
  11. From the Journal of the National Cancer Institute, Volume 100, No. 4, pp 277-281, published online 2/12/2008 by the Oxford University Press is of Muir-Torre Syndrome Among Lynch Syndrome Families bythe Division of Gastroenterology, Hepatology and Nutrition (CDS), Department of Pathology (WLF), and theHuman Cancer Genetics Program, Comprehensive Cancer Center (HH, IC, JAW, AdlC), of the Ohio StateUniversity-Columbus, OH;  specifically, Christopher D. South, Heather Hampel, Ilene Comeras, Judith A. Westman,Wendy L. Frankel and Albert de la Chapelle.
  12. From the Journal of Investigative Dermatology 7/6/2006, an excellent, comprehensive article on Muir Torre
  13.  Screening for Muir-Torre Syndrome Using Mismatch Repair Protein Immunohistochemistry of Sebaceous Neoplasms. IHC testing not recommended unless a personal history or family history of colorectal cancer exists   12/2012

  14. Brain Cancer and the Lynch Syndrome,Genetics Department, University of Helsinki, Finland,  September 2012

  15. Anaplastic oligodendroglioma in an adolescent with lynch syndrome, 12/19/2012  Queensland, Australia




  1. 7/11/2012  University of Padova, Padua Italy study concludes soft tissue sarcomas could be included In the spectrum of Lynch syndrome, that even if rarely, depend on MMR genes deficiency
  2. Unusual tumors associated with hereditary nonpolyposis colorectal cancer syndrome dated 2004 by MD Anderson concludes individuals with younger onset adrenal cortical carcinoma and anaplastic thyroid carcinoma should be tested for Lynch syndrome.
  3. Malignant Fibrous histiocytoma is a rare Lynch syndrome associated tumor in two German families: German study from Biomedical Research Laboratory, Johann Wolfgang-Goethe University, Frankfurt, Germany, dated 5/20/2011 concludes two patients within two different families with MSH-2 sustained a malignant fibrous histiocytoma.
  4. Sarcomas Associated With HNPCC, according to a study at the Clinical Research Center, Copenhagen, Denmark, dated 1/8/2009 .
  5. Thyroid Cancer In A Patient With A Germline In An MSH-2 Mutation.  Case report and Review Of The Lynch Syndrome Expanding Tumour Spectrum  Netherlands Observation
  6. Sloan Kettering Study --- Discussion of Unusual Cancers in Lynch Syndrome Including:  Peritoneal Mesothelioma; Pancreatic Neuroendocrine Tumor, Pancreatic Acinar Cell Carcinoma, and adrenalcortical carcinoma  7/2012
  7. Fibrous Histiocytoma discovered in two German families with MSH2.  (2038   and 932 +-  +3A >T)  Conclusion...Data further support that patients with Lynch syndrome are at increased risk for rare tumors such as MFH. However, the prognosis compared to sporadic MFH seems to be favorable.  9/2011
  8. A Molecularly Confirmed Neuroendocrine Tumor in Lynch Syndrome, Washington University, St. Louis, MO 7/2012