Synchronous breast cancers with different morphologic and molecular phenotypes occurring in lynch syndrome: What does the heterogeneity imply? Journal Article
| Authors: | D'arcy, C.; Wen, Y. H.; Stadler, Z. K.; Brogi, E.; Shia, J. |
| Article Title: | Synchronous breast cancers with different morphologic and molecular phenotypes occurring in lynch syndrome: What does the heterogeneity imply? |
| Abstract: | The increasingly widespread use of immunohistochemistry in the detection of DNA mismatch repair proteins has led to the observation of various unusual tumor types that occur in Lynch syndrome and exhibit mismatch repair protein deficiency. Understanding the clinical significance of such unusual tumors has become increasingly desirable. Here, we report a case of 2 synchronous breast cancers occurring in a 74-year-old woman who carried a deleterious germline mutation in MSH2 and who survived an endometrial and a colonic carcinoma. Both breast cancers were of lobular type with similar expression patterns for estrogen receptor, progesterone receptor, and Her2/neu. However, the 2 cancers differed in other characteristics. One tumor showed a solid alveolar histologic pattern with prominent tumor-infiltrating lymphocytes and loss of MSH2 and MSH6 protein on immunohistochemical staining. In contrast, the other tumor was of classic type with no apparent lymphocytic infiltration and no loss of mismatch repair protein. Such a case carries practical implications as it suggests that certain breast cancers may serve as tissue samples for the detection of mismatch repair deficiency in families at high risk for Lynch syndrome, thus expanding the test sample repertoire for genetic workup in these families. Furthermore, the case exemplifies the complexity of tumorigenesis in Lynch syndrome patients. The observation that, of the 2 breast cancers, increased tumor-infiltrating lymphocytes were present only in the tumor that showed mismatch repair protein abnormality is in keeping with what has been observed in the colon and other sites. Such persistent genotype-phenotype correlation across different organs affords the promise that molecular classification may allow identification of biologically distinct tumor subsets beyond the confines of the tumor's primary anatomic location. © 2011 Lippincott Williams & Wilkins. |
| Keywords: | immunohistochemistry; aged; dna binding protein; genetics; mutation; dna-binding proteins; case report; tumor associated leukocyte; lymphocytes, tumor-infiltrating; phenotype; tumor markers, biological; genotype; pathology; breast neoplasms; tumor marker; chemistry; mismatch repair; microsatellite instability; dna mismatch repair; nucleotide sequence; breast tumor; lung carcinoma; dna mutational analysis; protein msh2; multiple cancer; colorectal neoplasms, hereditary nonpolyposis; neoplasms, multiple primary; g t mismatch binding protein; g-t mismatch-binding protein; msh2 protein, human; muts homolog 2 protein; germ-line mutation; hereditary nonpolyposis colorectal cancer; carcinoma, lobular; hereditary nonpolyposis colorectal cancer syndrome; lobular breast carcinoma; mismatch repair defi-ciency |
| Journal Title: | American Journal of Surgical Pathology |
| Volume: | 35 |
| Issue: | 11 |
| ISSN: | 0147-5185 |
| Publisher: | Lippincott Williams & Wilkins |
| Date Published: | 2011-11-01 |
| Start Page: | 1743 |
| End Page: | 1748 |
| Language: | English |
| DOI: | 10.1097/PAS.0b013e3182320cff |
| PROVIDER: | scopus |
| PUBMED: | 21997695 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 9 December 2011" - "CODEN: AJSPD" - "Source: Scopus" |
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