title: Distinguishing primary from secondary mucinous ovarian tumors: an algorithm using the novel marker DPEP1.
abstract: Distinguishing primary mucinous ovarian cancers from ovarian metastases of digestive organ cancers is often challenging. Dipeptidase 1 was selected as the candidate novel marker of colorectal cancer based on an analysis of a gene expression microarray. Immunohistochemical analysis indicated that 13/16 ovarian metastases of colorectal cancers, but only 1/58 primary mucinous ovarian cancers, were dipeptidase 1-positive (threshold; ≧25% expression, P<0.0001). Next, five immunohistochemical markers (dipeptidase 1, estrogen receptor-α, cytokeratin 7, cytokeratin 20, and caudal type homeobox 2) were analyzed in combination. In a hierarchical clustering analysis, the mutually exclusive expression of cytokeratin 7 and dipeptidase 1 specifically identified the ovarian metastases of colorectal cancers (P<0.0001). In a decision tree analysis, cytokeratin 7, caudal type homeobox 2, and dipeptidase 1 classified primary mucinous ovarian cancers and ovarian metastases of digestive organ cancers with 90% accuracy. Finally, the five immunohistochemical markers were combined with six preoperative factors (patient's age, tumor size, laterality, serum CEA, CA19-9, and CA125) and combinations were analyzed. Of the 11 factors, 4 (dipeptidase 1, cytokeratin 7, caudal type homeobox 2, and tumor size) were used to generate a decision tree to classify primary mucinous ovarian cancers and metastases of digestive organ cancers with 93% accuracy. In conclusion, we identified a novel immunohistochemical marker, dipeptidase 1, to distinguish primary mucinous ovarian cancers from ovarian metastasis of colorectal cancers. The algorithm using immunohistochemical and clinical factors to distinguish metastases of digestive organ cancers from primary mucinous ovarian cancers will be useful to establish a protocol for the diagnosis of ovarian metastasis.
authors.affiliation: Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Japan.
authors.forename: Takako
authors.initials: T
authors.lastname: Okamoto
authors.forename: Noriomi
authors.initials: N
authors.lastname: Matsumura
authors.forename: Masaki
authors.initials: M
authors.lastname: Mandai
authors.forename: Tomonori
authors.initials: T
authors.lastname: Oura
authors.forename: Yukio
authors.initials: Y
authors.lastname: Yamanishi
authors.forename: Akiko
authors.initials: A
authors.lastname: Horiuchi
authors.forename: Junzo
authors.initials: J
authors.lastname: Hamanishi
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Baba
authors.forename: Masafumi
authors.initials: M
authors.lastname: Koshiyama
authors.forename: Tanri
authors.initials: T
authors.lastname: Shiozawa
authors.forename: Ikuo
authors.initials: I
authors.lastname: Konishi
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000378:metabolism* / Q000473:pathology* / Q000556:secondary; D000328:Adult; D000465:Algorithms; D014408:Biomarkers, Tumor / Q000378:metabolism; D016000:Cluster Analysis; D003937:Diagnosis, Differential; D004150:Dipeptidases / Q000378:metabolism*; D005260:Female; D058851:GPI-Linked Proteins / Q000378:metabolism; D005770:Gastrointestinal Neoplasms / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000556:secondary
chemical_list: D014408:Biomarkers, Tumor; D058851:GPI-Linked Proteins; D004150:Dipeptidases; C549872:dipeptidase 1