Comprehensive Clinicopathologic and Updated Immunohistochemical Characterization of Primary Ovarian Mucinous Carcinoma

The distinction of primary mucinous ovarian carcinoma (PMOC) from other primaries or secondaries is essential for selecting therapeutic options and prognostication. We aimed to characterize the immunohistochemical profile of 36 PMOCs using an extended immunohistochemical panel, with clinicopathologic features and outcome. PAX8 was negative in 30 (83.3%), and SATB2 was negative in 32/35. HNF1B, AMACR, and napsin-A were detected in 33 (91.7%), 35 (97.2%), and 0 (0%), respectively. MMR proteins and ARID1A were retained in 100%; PTEN was lost in 4 (11.1%). P53 was aberrant in 10 (27.8%); none overexpressed p16. HER2 was positive in 6/35 (17.1%). Most PMOCs had a favorable outcome. However, recurrence is usually fatal. The typical tumor profile was CK7+, CK20+/−, CDX2+/−, PAX8−, ER−, PgR−, and SATB2−. HER2 positivity suggests a possible target for therapy in advanced disease.

[1]  M. Köbel,et al.  Association of Hormone Receptor Expression with Survival in Ovarian Endometrioid Carcinoma: Biological Validation and Clinical Implications , 2017, International journal of molecular sciences.

[2]  M. Köbel,et al.  Significant frequency of MSH2/MSH6 abnormality in ovarian endometrioid carcinoma supports histotype‐specific Lynch syndrome screening in ovarian carcinomas , 2016, Histopathology.

[3]  N. Rosenfeld,et al.  Optimized p53 immunohistochemistry is an accurate predictor of TP53 mutation in ovarian carcinoma , 2016, The journal of pathology. Clinical research.

[4]  C. Parra‐Herran,et al.  Immunohistochemical characterization of appendiceal mucinous neoplasms and the value of special AT‐rich sequence‐binding protein 2 in their distinction from primary ovarian mucinous tumours , 2016, Histopathology.

[5]  A. Giassi,et al.  Immunohistochemistry in the Diagnosis of Mucinous Neoplasms Involving the Ovary: The Added Value of SATB2 and Biomarker Discovery Through Protein Expression Database Mining , 2016, International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists.

[6]  Kay J. Park,et al.  A Detailed Immunohistochemical Analysis of a Large Series of Cervical and Vaginal Gastric-type Adenocarcinomas , 2016, The American journal of surgical pathology.

[7]  S. Leung,et al.  An Immunohistochemical Algorithm for Ovarian Carcinoma Typing , 2016, International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists.

[8]  Grace E. Kim,et al.  SATB2 Expression Distinguishes Ovarian Metastases of Colorectal and Appendiceal Origin From Primary Ovarian Tumors of Mucinous or Endometrioid Type , 2016, The American journal of surgical pathology.

[9]  I. Hagemann,et al.  Clinical Outcomes among Women with Mucinous Adenocarcinoma of the Ovary , 2015, Gynecologic and Obstetric Investigation.

[10]  Ming-Yung Lee,et al.  Assessment of HER2 Status Using Immunohistochemistry (IHC) and Fluorescence In Situ Hybridization (FISH) Techniques in Mucinous Epithelial Ovarian Cancer: A Comprehensive Comparison between ToGA Biopsy Method and ToGA Surgical Specimen Method , 2015, PloS one.

[11]  F. Lu,et al.  Immunophenotypic Analysis in Early Müllerian Serous Carcinogenesis , 2015, International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists.

[12]  J. Vilchis,et al.  The value of SATB2 in the differential diagnosis of intestinal-type mucinous tumors of the ovary: primary vs metastatic. , 2015 .

[13]  M. Uhlén,et al.  Prognostic and treatment predictive significance of SATB1 and SATB2 expression in pancreatic and periampullary adenocarcinoma , 2014, Journal of Translational Medicine.

[14]  H. Ahn,et al.  Lynch Syndrome in patients with clear cell and endometrioid cancers of the ovary. , 2014, Gynecologic oncology.

[15]  A. Tinker,et al.  Molecular characterization of mucinous ovarian tumours supports a stratified treatment approach with HER2 targeting in 19% of carcinomas , 2013, The Journal of pathology.

[16]  I. Shih,et al.  Pathogenesis and the Role of ARID1A Mutation in Endometriosis-related Ovarian Neoplasms , 2013, Advances in anatomic pathology.

[17]  片桐 敦子.  Loss of ARID1A expression is related to shorter progression-free survival and chemoresistance in ovarian clear cell carcinoma , 2013 .

[18]  B. Clarke,et al.  Prevalence of Loss of Expression of DNA Mismatch Repair Proteins in Primary Epithelial Ovarian Tumors , 2012, International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists.

[19]  Boping Zhou,et al.  Exome sequencing of hepatitis B virus–associated hepatocellular carcinoma , 2012, Nature Genetics.

[20]  P. Tonin,et al.  An integrated genomic approach identifies ARID1A as a candidate tumor-suppressor gene in breast cancer , 2012, Oncogene.

[21]  H. Tsuda,et al.  Loss of ARID1A protein expression occurs as an early event in ovarian clear-cell carcinoma development and frequently coexists with PIK3CA mutations , 2012, Modern Pathology.

[22]  A. Noske,et al.  Loss of ARID1A/BAF250a-expression in endometriosis: a biomarker for risk of carcinogenic transformation? , 2012, Modern Pathology.

[23]  R. Pai,et al.  HER2 Expression in Gastric and Gastroesophageal Junction Adenocarcinoma in a US Population: Clinicopathologic Analysis With Proposed Approach to HER2 Assessment , 2012, Applied immunohistochemistry & molecular morphology : AIMM.

[24]  G. Mills,et al.  Clinical Assessment of PTEN Loss in Endometrial Carcinoma: Immunohistochemistry Out-Performs Gene Sequencing , 2011, Modern Pathology.

[25]  Meng Li,et al.  Somatic Mutations in the Chromatin Remodeling Gene ARID1A Occur in Several Tumor Types , 2011, Human mutation.

[26]  M. Post.  Mutation and Loss of Expression of ARID1A in Uterine Low-grade Endometrioid Carcinoma , 2012 .

[27]  Tian-Li Wang,et al.  ARID1A, a factor that promotes formation of SWI/SNF-mediated chromatin remodeling, is a tumor suppressor in gynecologic cancers. , 2011, Cancer research.

[28]  W. Cliby,et al.  Risk factors for lymph node metastasis in apparent early-stage epithelial ovarian cancer: implications for surgical staging. , 2011, Gynecologic oncology.

[29]  O. Kallioniemi,et al.  SATB2 in Combination With Cytokeratin 20 Identifies Over 95% of all Colorectal Carcinomas , 2011, The American journal of surgical pathology.

[30]  M. Loda,et al.  A Comprehensive Analysis of PAX8 Expression in Human Epithelial Tumors , 2011, The American journal of surgical pathology.

[31]  S. Leung,et al.  Calculator for ovarian carcinoma subtype prediction , 2011, Modern Pathology.

[32]  S. Lele,et al.  Advanced stage mucinous adenocarcinoma of the ovary is both rare and highly lethal , 2011, Cancer.

[33]  I. Shih,et al.  Clinicopathological Significance of Loss of ARID1A Immunoreactivity in Ovarian Clear Cell Carcinoma , 2010, International journal of molecular sciences.

[34]  A. Sood,et al.  Prevalence of Lymph Node Metastasis in Primary Mucinous Carcinoma of the Ovary , 2010, Obstetrics and gynecology.

[35]  D. Huntsman,et al.  Differences in Tumor Type in Low-stage Versus High-stage Ovarian Carcinomas , 2010, International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists.

[36]  M. Köbel,et al.  Primary Ovarian Mucinous Carcinoma of Intestinal Type: Significance of Pattern of Invasion and Immunohistochemical Expression Profile in a Series of 31 Cases , 2010, International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists.

[37]  Anna Adamiak,et al.  HER2 overexpression and amplification is present in a subset of ovarian mucinous carcinomas and can be targeted with trastuzumab therapy , 2009, BMC Cancer.

[38]  D. Rosen,et al.  Loss of DNA mismatch repair protein hMSH6 in ovarian cancer is histotype-specific. , 2008, International journal of clinical and experimental pathology.

[39]  A. Måsbäck,et al.  Ovarian cancer at young age: the contribution of mismatch‐repair defects in a population‐based series of epithelial ovarian cancer before age 40 , 2007, International journal of gynecological cancer : official journal of the International Gynecological Cancer Society.

[40]  A. Dansonka-Mieszkowska,et al.  PTEN mutation, expression and LOH at its locus in ovarian carcinomas. Relation to TP53, K-RAS and BRCA1 mutations. , 2006, Gynecologic oncology.

[41]  A. Gown,et al.  Immunohistochemical expression of CDX2 in primary ovarian mucinous tumors and metastatic mucinous carcinomas involving the ovary: comparison with CK20 and correlation with coordinate expression of CK7 , 2006, Modern Pathology.

[42]  H. Kajiyama,et al.  Clinical characteristics and prognosis of mucinous tumors of the ovary. , 2006, Gynecologic oncology.

[43]  M. Fraser,et al.  Over-expression of PTEN sensitizes human ovarian cancer cells to cisplatin-induced apoptosis in a p53-dependent manner. , 2006, Gynecologic oncology.

[44]  E. Moran,et al.  Nomenclature of the ARID family of DNA-binding proteins. , 2005, Genomics.

[45]  Y. Yen,et al.  Immunohistochemical Staining in the Diagnosis of Pancreatobiliary and Ampulla of Vater Adenocarcinoma: Application of CDX2, CK17, MUC1, and MUC2 , 2005, The American journal of surgical pathology.

[46]  D. Cao,et al.  Expression of Mesothelin, Fascin, and Prostate Stem Cell Antigen in Primary Ovarian Mucinous Tumors and Their Utility in Differentiating Primary Ovarian Mucinous Tumors From Metastatic Pancreatic Mucinous Carcinomas in the Ovary , 2005, International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists.

[47]  A. Gown,et al.  CDX2, a Highly Sensitive and Specific Marker of Adenocarcinomas of Intestinal Origin: An Immunohistochemical Survey of 476 Primary and Metastatic Carcinomas , 2003, The American journal of surgical pathology.

[48]  M. Stoler,et al.  Expression of cytokeratins 7 and 20 in ovarian neoplasia. , 2002, American journal of clinical pathology.

[49]  J. Mecklin,et al.  The clinical features of ovarian cancer in hereditary nonpolyposis colorectal cancer. , 2001, Gynecologic oncology.

[50]  S. Cannistra,et al.  Frequent loss of PTEN expression is linked to elevated phosphorylated Akt levels, but not associated with p27 and cyclin D1 expression, in primary epithelial ovarian carcinomas. , 2001, The American journal of pathology.

[51]  S. Silverberg.  Histopathologic grading of ovarian carcinoma: a review and proposal. , 2000, International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists.

[52]  G. Ueda,et al.  Immunohistochemical study of cytokeratin 7 for the differential diagnosis of adenocarcinomas in the ovary. , 1993, Gynecologic oncology.

[53]  R. Scully,et al.  Ovarian mullerian mucinous papillary cystadenomas of borderline malignancy. A clinicopathologic analysis , 1988, Cancer.

[54]  W. McGuire,et al.  Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. , 1987, Science.