title: A panel of antibodies to determine site of origin and malignancy in smooth muscle tumors.
abstract: Leiomyosarcomas are malignant smooth muscle tumors that occur most commonly in the gynecologic tract and soft tissue. There are different diagnostic criteria of malignancy for smooth muscle tumors arising at gynecologic and soft tissue sites and they may be managed differently but determining the primary site of a smooth muscle tumor can be difficult in some cases. In addition, the distinction between malignant and benign gynecologic tract smooth muscle tumors on morphologic grounds can be challenging. Using a series of tissue microarrays that contain 245 cases of leiomyosarcomas (102 gynecologic) with survival data, and 49 cases of uterine leiomyoma, we examined the ability of selected immune-markers (estrogen receptor (ER) and WT1) to distinguish between leiomyosarcomas of gynecologic and nongynecologic origin. In addition, we examined whether immunostains for p16, p53 and Ki-67 could distinguish between malignant and benign gynecologic smooth muscle tumors. ER nuclear positivity was observed in 3 and 50% of the nongynecologic and gynecologic leiomyosarcomas, respectively (P<0.001). Nuclear WT1 positivity was seen in 0 and 8% of the nongynecologic and gynecologic leiomyosarcomas, respectively (P<0.001). 87% of primary gynecologic leiomyosarcomas and 2% of uterine leiomyomas showed diffuse (>or=50% of cells) p16 staining (P<0.001). 23% of gynecologic leiomyosarcomas showed p53 immunopositivity (>or=50% of cells) whereas none of the leiomyomas were positive for p53 (P<0.001). 65% of the gynecologic leiomyosarcomas and 0% of the leiomyomas exhibited >10% Ki-67 proliferation index (P<0.001). Diffuse p16 and p53 immunopositivity and high Ki-67 proliferation index, singly or in combination, yielded an overall sensitivity of 92% and specificity of 98% for distinguishing between gynecologic leiomyosarcomas and leiomyomas and can be used as indicators of malignancy for gynecologic smooth muscle tumors. Although ER positivity can be used to support the gynecologic origin of a leiomyosarcomas, nuclear WT1 immunostaining is of little use.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver General Hospital, Vancouver, BC, Canada.
authors.forename: Cheng-Han
authors.initials: CH
authors.lastname: Lee
authors.forename: Dmitry A
authors.initials: DA
authors.lastname: Turbin
authors.forename: Y-C Vanessa
authors.initials: YC
authors.lastname: Sung
authors.forename: Inigo
authors.initials: I
authors.lastname: Espinosa
authors.forename: Kelli
authors.initials: K
authors.lastname: Montgomery
authors.forename: Matt
authors.initials: M
authors.lastname: van de Rijn
authors.forename: C Blake
authors.initials: CB
authors.lastname: Gilks
mesh_terms: D000328:Adult; D000906:Antibodies; D014408:Biomarkers, Tumor / Q000032:analysis; D002170:Canada; D002467:Cell Nucleus / Q000737:chemistry; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis; D003937:Diagnosis, Differential; D005060:Europe; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000032:analysis; D007889:Leiomyoma / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D007890:Leiomyosarcoma / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D019042:Muscle Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D009130:Muscle, Smooth / Q000737:chemistry* / Q000473:pathology; D011237:Predictive Value of Tests; D011960:Receptors, Estrogen / Q000032:analysis; D012680:Sensitivity and Specificity; D046888:Tissue Array Analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D014481:United States; D014594:Uterine Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D025721:WT1 Proteins / Q000032:analysis* / Q000276:immunology
chemical_list: D000906:Antibodies; D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D019394:Ki-67 Antigen; D011960:Receptors, Estrogen; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D025721:WT1 Proteins