Skip to main content
SpringerLink
Log in

Breast and Gynecologic Tumors

  • Chapter
  • First Online:
Practical Oncologic Molecular Pathology

Part of the book series: Practical Anatomic Pathology ((PAP))

  • 1741 Accesses

Abstract

Recent advances in molecular biology and molecular techniques have led to a better understanding of biologic diversity of breast and gynecologic tumors, the refinement of molecular taxonomies, the development of novel prognostic and predictive molecular assays, and the identification of new therapeutic targets. Molecular testing has become increasingly important in the diagnosis and management of breast and gynecologic tumors in the era of precision medicine. In the first part of this chapter, by using the format of frequently asked questions (FAQ), we review the roles of molecular testing in breast and gynecologic pathology, the common hereditary syndromes associated with breast and gynecologic tumors, the molecular subclassifications of breast and endometrial cancers, as well as the common biomarkers and the commonly used molecular testing in breast and gynecologic tumors. These FAQs are an attempt to provide evidence-based answers to common questions from clinicians, pathologists and trainees. In the second part of this chapter, we present four cases to further illustrate the application of molecular testing in our daily practices on breast and gynecologic tumors.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 179.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. The Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature. 2012;490:61–70.

    Article  PubMed Central  CAS  Google Scholar 

  2. Castera L, Krieger S, Rousselin A, et al. Next-generation sequencing for the diagnosis of hereditary breast and ovarian cancer using genomic capture targeting multiple candidate genes. Eur J Hum Genet. 2014;22:1305–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Walsh T, Lee MK, Casadei S, et al. Detection of inherited pathogenic variants for breast and ovarian cancer using genomic capture and massively parallel sequencing. Proc Natl Acad Sci U S A. 2010;107:12629–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Walsh T, King MC. Ten genes for inherited breast cancer. Cancer Cell. 2007;11:103–5.

    Article  CAS  PubMed  Google Scholar 

  5. van der Groep P, van der Wall E, van Diest PJ. Pathology of hereditary breast cancer. Cell Oncol (Dordr). 2011;34:71–88.

    Article  CAS  Google Scholar 

  6. Honrado E, Benítez J, Palacios J. Histopathology of BRCA1- and BRCA2-associated breast cancer. Crit Rev Oncol Hematol. 2006;59:27–39.

    Article  PubMed  Google Scholar 

  7. NCCN Clinical Practice Guidelines in Oncology-Breast Cancer Version 2020. https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf. Accessed 10 Dec 2020.

    Google Scholar 

  8. Manahan ER, Kuerer HM, Sebastian M, et al. Consensus guidelines on genetic testing for hereditary breast cancer from the American Society of Breast Surgeons. Ann Surg Oncol. 2019;26:3025–31.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Taylor A, Brady AF, Frayling IM, et al. Consensus for genes to be included on cancer panel tests offered by UK genetics services: guidelines of the UK Cancer genetics group. J Med Genet. 2018;55:372–7.

    Article  PubMed  Google Scholar 

  10. Harris LN, Ismaila N, McShane LM, et al. Use of biomarkers to guide decisions on adjuvant systemic therapy for women with early-stage invasive breast Cancer: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2016;34:1134–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Perou CM, Sørlie T, Eisen MB, et al. Molecular portraits of human breast tumours. Nature. 2000;406:747–52.

    Article  CAS  PubMed  Google Scholar 

  12. Sørlie T, Perou CM, Tibshirani R, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A. 2001;98:10869–74.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Sorlie T, Tibshirani R, Parker J, et al. Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci U S A. 2003;100:8418–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Sørlie T. Molecular classification of breast tumors: toward improved diagnostics and treatments. Methods Mol Biol. 2007;360:91–114.

    PubMed  Google Scholar 

  15. Hennessy BT, Gonzalez-Angulo AM, Stemke-Hale K, et al. Characterization of a naturally occurring breast cancer subset enriched in epithelial-to-mesenchymal transition and stem cell characteristics. Cancer Res. 2009;69:4116–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Prat A, Parker JS, Karginova O, et al. Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer. Breast Cancer Res. 2010;12:R68.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Farmer P, Bonnefoi H, Becette V, et al. Identification of molecular apocrine breast tumours by microarray analysis. Oncogene. 2005;24:4660–71.

    Article  CAS  PubMed  Google Scholar 

  18. Vuong D, Simpson PT, Green B, Cummings MC, Lakhani SR. Molecular classification of breast cancer. Virchows Arch. 2014;465:1–14.

    Article  CAS  PubMed  Google Scholar 

  19. Fragomeni SM, Sciallis A, Jeruss JS. Molecular subtypes and local-regional control of breast cancer. Surg Oncol Clin N Am. 2018;27:95–120.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Groenendijk FH, Treece T, Yoder E, et al. Estrogen receptor variants in ER-positive basal-type breast cancers responding to therapy like ER-negative breast cancers. NPJ Breast Cancer. 2019;5:15.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Beitsch P, Whitworth P, Baron P, et al. Pertuzumab/Trastuzumab/CT versus Trastuzumab/CT therapy for HER2+ breast cancer: results from the prospective neoadjuvant breast registry symphony trial (NBRST). Ann Surg Oncol. 2017;24:2539–46.

    Article  PubMed  Google Scholar 

  22. Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thürlimann B, Senn HJ, Panel members. Strategies for subtypes--dealing with the diversity of breast cancer: highlights of the St. Gallen international expert consensus on the primary therapy of early breast Cancer 2011. Ann Oncol. 2011;22:1736–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Lehmann BD, Bauer JA, Chen X, et al. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest. 2011;121:2750–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Lehmann BD, Jovanović B, Chen X, et al. Refinement of triple-negative breast cancer molecular subtypes: implications for neoadjuvant chemotherapy selection. PLoS One. 2016;11:e0157368.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Bertucci F, Finetti P, Cervera N, et al. How basal are triple-negative breast cancers? Int J Cancer. 2008;123:236–40.

    Article  CAS  PubMed  Google Scholar 

  26. Alluri P, Newman LA. Basal-like and triple-negative breast cancers: searching for positives among many negatives. Surg Oncol Clin N Am. 2014;23:567–77.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Allison KH, Hammond MEH, Dowsett M, et al. Estrogen and progesterone receptor testing in breast cancer: ASCO/CAP guideline update. J Clin Oncol. 2020;38:1346–66.

    Article  PubMed  Google Scholar 

  28. Wolff AC, Hammond MEH, Allison KH, et al. Human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline focused update. J Clin Oncol. 2018;36:2105–22.

    Article  CAS  PubMed  Google Scholar 

  29. Cui X, Schiff R, Arpino G, Osborne CK, Lee AV. Biology of progesterone receptor loss in breast cancer and its implications for endocrine therapy. J Clin Oncol. 2005;23:7721–35.

    Article  CAS  PubMed  Google Scholar 

  30. Allison KH. Ancillary prognostic and predictive testing in breast cancer: focus on discordant, unusual, and borderline results. Surg Pathol Clin. 2018;11:147–76.

    Article  PubMed  Google Scholar 

  31. van de Ven S, Smit VT, Dekker TJ, Nortier JW, Kroep JR. Discordances in ER, PR and HER2 receptors after neoadjuvant chemotherapy in breast cancer. Cancer Treat Rev. 2011;37:422–30.

    PubMed  Google Scholar 

  32. Zhang H, Moisini I, Ajabnoor RM, Turner BM, Hicks DG. Applying the new guidelines of HER2 testing in breast cancer. Curr Oncol Rep. 2020;22:51.

    Article  PubMed  Google Scholar 

  33. Sahoo S, Dabbs DJ, Bhargava R. Pathology of neoadjuvant therapeutic response of breast carcinoma. In: Dabbs, editor. Breast pathology. 2nd ed. Philadelphia: Elsevier Inc. 2016.

    Google Scholar 

  34. Kasami M, Uematsu T, Honda M, et al. Comparison of estrogen receptor, progesterone receptor and HER-2 status in breast cancer pre- and post-neoadjuvant chemotherapy. Breast. 2008;17:523–7.

    Article  PubMed  Google Scholar 

  35. Li P, Liu T, Wang Y, et al. Influence of neoadjuvant chemotherapy on HER2/neu status in invasive breast cancer. Clin Breast Cancer. 2013;13:53–60.

    Article  CAS  PubMed  Google Scholar 

  36. van Es SC, van der Vegt B, Bensch F, et al. Decalcification of breast cancer bone metastases with EDTA does not affect ER, PR, and HER2 results. Am J Surg Pathol. 2019;43:1355–60.

    Article  PubMed  Google Scholar 

  37. Frequently Asked Questions for Human Epidermal Growth Factor Receptor 2 (HER2) Testing in Breast Cancer: ASCO/CAP Clinical Practice Guideline Focused Update. https://www.cap.org/protocols-and-guidelines/cap-guidelines/current-cap-guidelines/recommendations-for-human-epidermal-growth-factor-2-testing-in-breast-cancer. Accessed 10 Dec 2020.

  38. Zhang Z, Wang J, Skinner KA, et al. Pathological features and clinical outcomes of breast cancer according to levels of oestrogen receptor expression. Histopathology. 2014;65:508–16.

    Article  PubMed  Google Scholar 

  39. Raghav KP, Hernandez-Aya LF, Lei X, et al. Impact of low estrogen/progesterone receptor expression on survival outcomes in breast cancers previously classified as triple negative breast cancers. Cancer. 2012;118:1498–506.

    Article  CAS  PubMed  Google Scholar 

  40. Gloyeske NC, Dabbs DJ, Bhargava R. Low ER+ breast cancer: is this a distinct group? Am J Clin Pathol. 2014;141:697–701.

    Article  PubMed  Google Scholar 

  41. Kraus JA, Dabbs DJ, Beriwal S, Bhargava R. Semi-quantitative immunohistochemical assay versus oncotype DX(®) qRT-PCR assay for estrogen and progesterone receptors: an independent quality assurance study. Mod Pathol. 2012;25:869–76.

    Article  CAS  PubMed  Google Scholar 

  42. Badve SS, Baehner FL, Gray RP, et al. Estrogen- and progesterone-receptor status in ECOG 2197: comparison of immunohistochemistry by local and central laboratories and quantitative reverse transcription polymerase chain reaction by central laboratory. J Clin Oncol. 2008;26:2473–81.

    Article  PubMed  Google Scholar 

  43. Furrer D, Sanschagrin F, Jacob S, Diorio C. Advantages and disadvantages of technologies for HER2 testing in breast cancer specimens. Am J Clin Pathol. 2015;144:686–703.

    Article  CAS  PubMed  Google Scholar 

  44. Press MF, Seoane JA, Curtis C, et al. Assessment of ERBB2/HER2 status in HER2-equivocal breast cancers by FISH and 2013/2014 ASCO-CAP guidelines. JAMA Oncol. 2019;5:366–75.

    Article  PubMed  Google Scholar 

  45. Sneige N, Hess KR, Multani AS, Gong Y, Ibrahim NK. Prognostic significance of equivocal human epidermal growth factor receptor 2 results and clinical utility of alternative chromosome 17 genes in patients with invasive breast cancer: a cohort study. Cancer. 2017;123:1115–23.

    Article  CAS  PubMed  Google Scholar 

  46. Yu J, Dabbs DJ, Shuai Y, Niemeier LA, Bhargava R. Classical-type invasive lobular carcinoma with HER2 overexpression: clinical, histologic, and hormone receptor characteristics. Am J Clin Pathol. 2011;136:88–97.

    Article  CAS  PubMed  Google Scholar 

  47. Zhang H, Moisini I, Ajabnoor RM, et al. Frequency, clinicopathologic characteristics, and follow-up of HER2-positive nonpleomorphic invasive lobular carcinoma of the breast. Am J Clin Pathol. 2020;153:583–92.

    Article  CAS  PubMed  Google Scholar 

  48. Schrijver WA, Suijkerbuijk KP, van Gils CH, van der Wall E, Moelans CB, van Diest PJ. Receptor conversion in distant breast cancer metastases: a systematic review and meta-analysis. J Natl Cancer Inst. 2018;110:568–80.

    Article  PubMed  Google Scholar 

  49. Woo JW, Chung YR, Ahn S, et al. Changes in biomarker status in metastatic breast cancer and their prognostic value. J Breast Cancer. 2019;22:439–52.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Sabine V, Crozier C, Brookes C, et al. Mutational analysis of PI3K/AKT signaling pathway in tamoxifen exemestane adjuvant multinational pathology study. J Clin Oncol. 2014;32:2951–8.

    Article  CAS  PubMed  Google Scholar 

  51. Andre F, Ciruelos E, Rubovszky G, et al. Alpelisib for PIK3CA-mutated, hormone receptor-positive advanced breast cancer. N Engl J Med. 2019;380:1929–40.

    Article  CAS  PubMed  Google Scholar 

  52. Tognon C, Knezevich SR, Huntsman D, et al. Expression of the ETV6-NTRK3 gene fusion as a primary event in human secretory breast carcinoma. Cancer Cell. 2002;2:367–76.

    Article  CAS  PubMed  Google Scholar 

  53. Persson M, Andren Y, Mark J, et al. Recurrent fusion of MYB and NFIB transcription factor genes in carcinomas of the breast and head and neck. Proc Natl Acad Sci U S A. 2009;106:18740–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Cancer Genome Atlas Research Network. Integrated genomic analyses of ovarian carcinoma. Nature. 2011;474:609–15.

    Article  CAS  Google Scholar 

  55. Pennington KP, Walsh T, Harrell MI, et al. Germline and somatic mutations in homologous recombination genes predict platinum response and survival in ovarian, fallopian tube, and peritoneal carcinomas. Clin Cancer Res. 2014;20:764–75.

    Article  CAS  PubMed  Google Scholar 

  56. Farmer H, McCabe N, Lord CJ, et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature. 2005;434:917–21.

    Article  CAS  PubMed  Google Scholar 

  57. Fong PC, Boss DS, Yap TA, et al. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med. 2009;361:123–34.

    Article  CAS  PubMed  Google Scholar 

  58. Veeck J, Ropero S, Setien F, et al. BRCA1 CpG island hypermethylation predicts sensitivity to poly(adenosine diphosphate)-ribose polymerase inhibitors. J Clin Oncol. 2010;28:e563–4.

    Article  PubMed  Google Scholar 

  59. O’Connor MJ. Targeting the DNA damage response in cancer. Mol Cell. 2015;60:547–60.

    Article  PubMed  CAS  Google Scholar 

  60. Pennington KP, Swisher EM. Hereditary ovarian cancer: beyond the usual suspects. Gynecol Oncol. 2012;124:347–53.

    Article  CAS  PubMed  Google Scholar 

  61. Norquist BM, Harrell MI, Brady MF, et al. Inherited mutations in women with ovarian carcinoma. JAMA Oncol. 2016;2:482–90.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Davies H, Glodzik D, Morganella S, et al. HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures. Nat Med. 2017;23:517–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Cruz C, Castroviejo-Bermejo M, Gutiérrez-Enríquez S, et al. RAD51 foci as a functional biomarker of homologous recombination repair and PARP inhibitor resistance in germline BRCA-mutated breast cancer. Ann Oncol. 2018;29:1203–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Castroviejo-Bermejo M, Cruz C, Llop-Guevara A, et al. A RAD51 assay feasible in routine tumor samples calls PARP inhibitor response beyond BRCA mutation. EMBO Mol Med. 2018;10:e9172.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  65. Konstantinopoulos PA, Norquist B, Lacchetti C, et al. Germline and somatic tumor testing in epithelial ovarian cancer: ASCO guideline. J Clin Oncol. 2020;38:1222–45.

    Article  PubMed  Google Scholar 

  66. Dougherty BA, Lai Z, Hodgson DR, et al. Biological and clinical evidence for somatic mutations in BRCA1 and BRCA2 as predictive markers for olaparib response in high-grade serous ovarian cancers in the maintenance setting. Oncotarget. 2017;8:43653–61.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Merajver SD, Pham TM, Caduff RF, et al. Somatic mutations in the BRCA1 gene in sporadic ovarian tumours. Nat Genet. 1995;9:439–43.

    Article  CAS  PubMed  Google Scholar 

  68. Fraune C, Rosebrock J, Simon R, et al. High homogeneity of MMR deficiency in ovarian cancer. Gynecol Oncol. 2020;156:669–75.

    Article  CAS  PubMed  Google Scholar 

  69. Rambau PF, Duggan MA, Ghatage P, et al. Significant frequency of MSH2/MSH6 abnormality in ovarian endometrioid carcinoma supports histotype-specific Lynch syndrome screening in ovarian carcinomas. Histopathology. 2016;69:288–97.

    Article  PubMed  Google Scholar 

  70. Leskela S, Romero I, Cristobal E, et al. Mismatch repair deficiency in ovarian carcinoma: frequency, causes, and consequences. Am J Surg Pathol. 2020;44:649–56.

    Article  PubMed  Google Scholar 

  71. Rabban JT, Calkins SM, Karnezis AN, et al. Association of tumor morphology with mismatch-repair protein status in older endometrial cancer patients: implications for universal versus selective screening strategies for Lynch syndrome. Am J Surg Pathol. 2014;38:793–800.

    Article  PubMed  Google Scholar 

  72. Garg K, Soslow RA. Lynch syndrome (hereditary non-polyposis colorectal cancer) and endometrial carcinoma. J Clin Pathol. 2009;62:679–84.

    Article  CAS  PubMed  Google Scholar 

  73. Broaddus RR, Lynch HT, Chen LM, et al. Pathologic features of endometrial carcinoma associated with HNPCC: a comparison with sporadic endometrial carcinoma. Cancer. 2006;106:87–94.

    Article  CAS  PubMed  Google Scholar 

  74. Westin SN, Lacour RA, Urbauer DL, et al. Carcinoma of the lower uterine segment: a newly described association with Lynch syndrome. J Clin Oncol. 2008;26:5965–71.

    Article  PubMed  PubMed Central  Google Scholar 

  75. Hampel H, Frankel W, Panescu J, et al. Screening for Lynch syndrome (hereditary nonpolyposis colorectal cancer) among endometrial cancer patients. Cancer Res. 2006;66:7810–7.

    Article  CAS  PubMed  Google Scholar 

  76. Lu KH, Dinh M, Kohlmann W, et al. Gynecologic cancer as a “sentinel cancer” for women with hereditary nonpolyposis colorectal cancer syndrome. Obstet Gynecol. 2005;105:569–74.

    Article  PubMed  Google Scholar 

  77. Practice Bulletin No. 147. Lynch syndrome. Obstet Gynecol. 2014;124:1042–54.

    Article  Google Scholar 

  78. Mills AM, Longacre TA. Lynch syndrome screening in the gynecologic tract: current state of the art. Am J Surg Pathol. 2016;40:e35–44.

    Article  PubMed  Google Scholar 

  79. McConechy MK, Talhouk A, Li-Chang HH, et al. Detection of DNA mismatch repair (MMR) deficiencies by immunohistochemistry can effectively diagnose the microsatellite instability (MSI) phenotype in endometrial carcinomas. Gynecol Oncol. 2015;137:306–10.

    Article  CAS  PubMed  Google Scholar 

  80. Gan C, Love C, Beshay V, et al. Applicability of next generation sequencing technology in microsatellite instability testing. Genes (Basel). 2015;6(1):46–59.

    Article  CAS  Google Scholar 

  81. Salipante SJ, Scroggins SM, Hampel HL, Turner EH, Pritchard CC. Microsatellite instability detection by next generation sequencing. Clin Chem. 2014;60:1192–9.

    Article  CAS  PubMed  Google Scholar 

  82. Graham RP, Kerr SE, Butz ML, et al. Heterogenous MSH6 loss is a result of microsatellite instability within MSH6 and occurs in sporadic and hereditary colorectal and endometrial carcinomas. Am J Surg Pathol. 2015;39:1370–6.

    Article  PubMed  Google Scholar 

  83. Watkins JC, Nucci MR, Ritterhouse LL, Howitt BE, Sholl LM. Unusual mismatch repair immunohistochemical patterns in endometrial carcinoma. Am J Surg Pathol. 2016;40:909–16.

    Article  PubMed  Google Scholar 

  84. Stelloo E, Jansen AML, Osse EM, et al. Practical guidance for mismatch repair-deficiency testing in endometrial cancer. Ann Oncol. 2017;28:96–102.

    Article  CAS  PubMed  Google Scholar 

  85. Aird JJ, Steel MJ, Chow C, et al. Should you repeat mismatch repair testing in cases of tumour recurrence? An evaluation of repeat mismatch repair testing by the use of immunohistochemistry in recurrent tumours of the gastrointestinal and gynaecological tracts. Histopathology. 2020;76:521–30.

    Article  PubMed  Google Scholar 

  86. Ta RM, Hecht JL, Lin DI. Discordant loss of mismatch repair proteins in advanced endometrial endometrioid carcinoma compared to paired primary uterine tumors. Gynecol Oncol. 2018;151:401–6.

    Article  CAS  PubMed  Google Scholar 

  87. Boland CR, Thibodeau SN, Hamilton SR, et al. A National Cancer Institute workshop on microsatellite instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res. 1998;58:5248–57.

    CAS  PubMed  Google Scholar 

  88. Salipante SJ, Scroggins SM, Hampel HL, Turner EH, Pritchard CC. Microsatellite instability detection by next generation sequencing. Clin Chem. 2014;60:1192–9.

    Article  CAS  PubMed  Google Scholar 

  89. Middha S, Zhang L, Nafa K, et al. Reliable pan-cancer microsatellite instability assessment by using targeted next-generation sequencing data. JCO Precis Oncol. 2017;2017:PO.17.00084.

    Google Scholar 

  90. Gan C, Love C, Beshay V, et al. Applicability of next generation sequencing technology in microsatellite instability testing. Genes (Basel). 2015;6:46–59.

    Article  CAS  Google Scholar 

  91. Pang J, Gindin T, Mansukhani M, Fernandes H, Hsiao S. Microsatellite instability detection using a large next-generation sequencing cancer panel across diverse tumour types. J Clin Pathol. 2020;73:83–9.

    Article  CAS  PubMed  Google Scholar 

  92. Simpkins SB, Bocker T, Swisher EM, et al. MLH1 promoter methylation and gene silencing is the primary cause of microsatellite instability in sporadic endometrial cancers. Hum Mol Genet. 1999;8:661–6.

    Article  CAS  PubMed  Google Scholar 

  93. Bruegl AS, Djordjevic B, Urbauer DL, et al. Utility of MLH1 methylation analysis in the clinical evaluation of Lynch syndrome in women with endometrial cancer. Curr Pharm Des. 2014;20:1655–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Peterson LM, Kipp BR, Halling KC, et al. Molecular characterization of endometrial cancer: a correlative study assessing microsatellite instability, MLH1 hypermethylation, DNA mismatch repair protein expression, and PTEN, PIK3CA, KRAS, and BRAF mutation analysis. Int J Gynecol Pathol. 2012;31:195–205.

    Article  CAS  PubMed  Google Scholar 

  95. Yokoyama T, Takehara K, Sugimoto N, et al. Lynch syndrome-associated endometrial carcinoma with MLH1 germline mutation and MLH1 promoter hypermethylation: a case report and literature review. BMC Cancer. 2018;18:576.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  96. Rahner N, Friedrichs N, Steinke V, et al. Coexisting somatic promoter hypermethylation and pathogenic MLH1 germline mutation in Lynch syndrome. J Pathol. 2008;214:10–6.

    Article  CAS  PubMed  Google Scholar 

  97. Crucianelli F, Tricarico R, Turchetti D, et al. MLH1 constitutional and somatic methylation in patients with MLH1 negative tumors fulfilling the revised Bethesda criteria. Epigenetics. 2014;9:1431–8.

    Article  PubMed  PubMed Central  Google Scholar 

  98. Djordjevic B, Broaddus RR. Laboratory assays in evaluation of Lynch syndrome in patients with endometrial carcinoma. Surg Pathol Clin. 2016;9:289–99.

    Article  PubMed  PubMed Central  Google Scholar 

  99. Kuismanen SA, Moisio AL, Schweizer P, et al. Endometrial and colorectal tumors from patients with hereditary nonpolyposis colon cancer display different patterns of microsatellite instability. Am J Pathol. 2002;160:1953–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Berends MJ, Wu Y, Sijmons RH, et al. Molecular and clinical characteristics of MSH6 variants: an analysis of 25 index carriers of a germline variant. Am J Hum Genet. 2002;70:26–37.

    Article  CAS  PubMed  Google Scholar 

  101. Wagner A, Hendriks Y, Meijers-Heijboer EJ, et al. Atypical HNPCC owing to MSH6 germline mutations: analysis of a large Dutch pedigree. J Med Genet. 2001;38:318–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Wu Y, Berends MJ, Mensink RG, et al. Association of hereditary nonpolyposis colorectal cancer-related tumors displaying low microsatellite instability with MSH6 germline mutations. Am J Hum Genet. 1999;65:1291–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Rhees J, Arnold M, Boland CR. Inversion of exons 1-7 of the MSH2 gene is a frequent cause of unexplained Lynch syndrome in one local population. Familial Cancer. 2014;13:219–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Rumilla K, Schowalter KV, Lindor NM, et al. Frequency of deletions of EPCAM (TACSTD1) in MSH2-associated Lynch syndrome cases. J Mol Diagn. 2011;13:93–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Geurts-Giele WR, Leenen CH, Dubbink HJ, et al. Somatic aberrations of mismatch repair genes as a cause of microsatellite-unstable cancers. J Pathol. 2014;234:548–59.

    Article  CAS  PubMed  Google Scholar 

  106. Haraldsdottir S, Hampel H, Tomsic J, et al. Colon and endometrial cancers with mismatch repair deficiency can arise from somatic, rather than germline, mutations. Gastroenterology. 2014;147:1308–1316.e1.

    Article  PubMed  Google Scholar 

  107. Cancer Genome Atlas Research Network, Kandoth C, Schultz N, et al. Integrated genomic characterization of endometrial carcinoma. Nature. 2013;497:67–73.

    Article  CAS  Google Scholar 

  108. León-Castillo A, de Boer SM, Powell ME, et al. Molecular classification of the PORTEC-3 trial for high-risk endometrial Cancer: impact on prognosis and benefit from adjuvant therapy. J Clin Oncol. 2020;38:JCO2000549.

    Article  Google Scholar 

  109. McAlpine J, Leon-Castillo A, Bosse T. The rise of a novel classification system for endometrial carcinoma; integration of molecular subclasses. J Pathol. 2018;244:538–49.

    Article  PubMed  Google Scholar 

  110. Koontz JI, Soreng AL, Nucci M, et al. Frequent fusion of the JAZF1 and JJAZ1 genes in endometrial stromal tumors. Proc Natl Acad Sci U S A. 2001;98:6348–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Nucci MR, Harburger D, Koontz J, Dal Cin P, Sklar J. Molecular analysis of the JAZF1-JJAZ1 gene fusion by RT-PCR and fluorescence in situ hybridization in endometrial stromal neoplasms. Am J Surg Pathol. 2007;31:65–70.

    Article  PubMed  Google Scholar 

  112. Hoang L, Chiang S, Lee CH. Endometrial stromal sarcomas and related neoplasms: new developments and diagnostic considerations. Pathology. 2018;50:162–77.

    Article  CAS  PubMed  Google Scholar 

  113. Lee CH, Ou WB, Mariño-Enriquez A, et al. 14-3-3 fusion oncogenes in high-grade endometrial stromal sarcoma. Proc Natl Acad Sci U S A. 2012;109:929–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Lee CH, Ali RH, Rouzbahman M, et al. The clinicopathologic features of YWHAE-FAM22 endometrial stromal sarcomas: a histologically high-grade and clinically aggressive tumor. Am J Surg Pathol. 2012;36:1562–70.

    Article  PubMed  PubMed Central  Google Scholar 

  115. Conklin CM, Longacre TA. Endometrial stromal tumors: the new WHO classification. Adv Anat Pathol. 2014;21:383–93.

    Article  CAS  PubMed  Google Scholar 

  116. Buza N, Roque DM, Santin AD. HER2/neu in endometrial cancer: a promising therapeutic target with diagnostic challenges. Arch Pathol Lab Med. 2014;138:343–50.

    Article  PubMed  Google Scholar 

  117. Fader AN, Roque DM, Siegel E, et al. Randomized phase II trial of carboplatin-paclitaxel versus carboplatin-paclitaxel-Trastuzumab in uterine serous carcinomas that overexpress human epidermal growth factor receptor 2/neu. J Clin Oncol. 2018;36:2044–51.

    Article  CAS  PubMed  Google Scholar 

  118. Poljak M, Oštrbenk Valenčak A, Gimpelj Domjanič G, Xu L, Arbyn M. Commercially available molecular tests for human papillomaviruses: a global overview. Clin Microbiol Infect. 2020;26:1144. S1198-743X(20)30179-8

    Article  CAS  PubMed  Google Scholar 

  119. Salazar KL, Duhon DJ, Olsen R, Thrall M. A review of the FDA-approved molecular testing platforms for human papillomavirus. J Am Soc Cytopathol. 2019;8:284–92.

    Article  PubMed  Google Scholar 

  120. Darragh TM, Colgan TJ, Cox JT, et al. The lower Anogenital squamous terminology standardization project for HPV-associated lesions: background and consensus recommendations from the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology. Arch Pathol Lab Med. 2012;136:1266–97.

    Article  PubMed  Google Scholar 

  121. Rabban JT, Karnezis AN, Devine WP. Practical roles for molecular diagnostic testing in ovarian adult granulosa cell tumour, Sertoli-Leydig cell tumour, microcystic stromal tumour and their mimics. Histopathology. 2020;76:11–24.

    Article  PubMed  Google Scholar 

  122. Buza N, Hui P. Immunohistochemistry and other ancillary techniques in the diagnosis of gestational trophoblastic diseases. Semin Diagn Pathol. 2014;31:223–32.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA

    Huina Zhang & David G. Hicks

Authors
  1. Huina Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David G. Hicks
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Huina Zhang .

Editor information

Editors and Affiliations

  1. Department of Laboratory Medicine, Geisinger Health, Danville, PA, USA

    Yi Ding

  2. Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA

    Linsheng Zhang

Rights and permissions

Reprints and permissions

Copyright information

© 2021 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Zhang, H., Hicks, D.G. (2021). Breast and Gynecologic Tumors. In: Ding, Y., Zhang, L. (eds) Practical Oncologic Molecular Pathology. Practical Anatomic Pathology. Springer, Cham. https://doi.org/10.1007/978-3-030-73227-1_5

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-73227-1_5

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-73226-4

  • Online ISBN: 978-3-030-73227-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation