Abstract
CDX-2 is a caudal-type homeobox gene, encoding a transcription factor that plays an important role in proliferation and differentiation of intestinal epithelial cells. The utility of antibodies to CDX2 in the identification of adenocarcinomas of the gastrointestinal tract, particularly colorectal adenocarcinomas, in both primary and metastatic settings is well established. It is well-known that patients with testicular tumors may occasionally lack an obvious palpable mass. However, the expression of CDX2 in malignant germ cell tumors of the testes which have metastatic potential has not been previously studied in a large series. A tissue microarray was constructed from 52 malignant germ cell tumors of the testes including: 29 cases of classic seminoma, 8 cases of embryonal carcinoma, 8 cases of yolk sac tumor, 4 cases of malignant teratoma, 2 cases of choriocarcinoma, and 1 case of spermatocytic seminoma. Ten cases of intratubular germ cell neoplasia and seven cases of benign testicles with normal seminiferous tubules were also included in tissue microarray. Immunohistochemical stains for CDX2 was performed and analyzed. Only nuclear staining was considered positive. Positive expression of CDX2 was identified in 2/2 cases (100 %) of choriocarcinoma, 4/8 cases (50 %) of teratoma, 3/8 cases (38 %) of embryonal carcinoma, 3/8 cases (38 %) of yolk sac tumor, and 1/29 cases (3 %) of classic seminoma. CDX2 was negative in all cases of intratubular germ cell neoplasia, normal seminiferous tubules, and the only case of spermatocytic seminoma. The role of CDX-2 in the differentiation of intestinal/enteric epithelial cells may contribute to the formation of trophoblastic, glandular, villous, or cystic structures in germ cell tumors of the testes. This study suggests that the expression of CDX2 in a variety of malignant germ cell tumors of the testes may be a potential pitfall in metastatic tumors of unknown primary, which are thought to be of gastrointestinal/colorectal origin but are actually from a clinically occult testicular tumor.
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References
Stainier DY. No organ left behind: tales of gut development and evolution. Science. 2005;307(5717):1902–4.
Suh E, Traber PG. An intestine-specific homeobox gene regulates proliferation and differentiation. Mol Cell Biol. 1996;16(2):619–25.
Fraggetta F, Pelosi G, Cafici A, et al. CDX2 immunoreactivity in primary and metastatic ovarian mucinous tumours. Virchows Arch. 2003;443(6):782–6.
Houghton O, Connolly LE, McCluggage WG. Morules in endometrioid proliferations of the uterus and ovary consistently express the intestinal transcription factor CDX2. Histopathology. 2008;53(2):156–65.
Wani Y, Notohara K, Saegusa M, Tsukayama C. Aberrant Cdx2 expression in endometrial lesions with squamous differentiation: important role of Cdx2 in squamous morula formation. Hum Pathol. 2008;39(7):1072–9.
Jaffee IM, Rahmani M, Singhal MG, Younes M. Expression of the intestinal transcription factor CDX2 in carcinoid tumors is a marker of midgut origin. Arch Pathol Lab Med. 2006;130(10):1522–6.
Sullivan LM, Smolkin ME, Frierson Jr HF, Galgano MT. Comprehensive evaluation of CDX2 in invasive cervical adenocarcinomas: immunopositivity in the absence of overt colorectal morphology. Am J Surg Pathol. 2008;32(11):1608–12.
Herawi M, De Marzo AM, Kristiansen G, Epstein JI. Expression of CDX2 in benign tissue and adenocarcinoma of the prostate. Hum Pathol. 2007;38(1):72–8.
Devesa SS, Blot WJ, Stone BJ, et al. Recent cancer trends in the United States. J Natl Cancer Inst. 1995;87(3):175–82.
Wu X, Groves FD, McLaughlin CC, et al. Cancer incidence patterns among adolescents and young adults in the United States. Cancer Causes Control. 2005;16(3):309–20.
Talerman A. Germ cell tumours. Ann Pathol. 1985;5(3):145–57.
Bergstrom R, Adami HO, Mohner M, et al. Increase in testicular cancer incidence in six European countries: a birth cohort phenomenon. J Natl Cancer Inst. 1996;88(11):727–33.
Zheng T, Holford TR, Ma Z, et al. Continuing increase in incidence of germ-cell testis cancer in young adults: experience from Connecticut, USA, 1935–1992. Int J Cancer. 1996;65(6):723–9.
Ye H, Ulbright TM. Difficult differential diagnoses in testicular pathology. Arch Pathol Lab Med. 2012;136(4):435–46.
Ulbright TM, Young RH, Scully RE. Trophoblastic tumors of the testis other than classic choriocarcinoma: “monophasic” choriocarcinoma and placental site trophoblastic tumor: a report of two cases. Am J Surg Pathol. 1997;21(3):282–8.
Ulbright TM. Germ cell tumors of the gonads: a selective review emphasizing problems in differential diagnosis, newly appreciated, and controversial issues. Mod Pathol. 2005;18 Suppl 2:S61–79.
Kao CS, Idrees MT, Young RH, Ulbright TM. Solid pattern yolk sac tumor: a morphologic and immunohistochemical study of 52 cases. Am J Surg Pathol. 2012;36(3):360–7.
Bing Z, Pasha T, Tomaszewski JE, Zhang P. CDX2 expression in yolk sac component of testicular germ cell tumors. Int J Surg Pathol. 2009;17(5):373–7.
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Lee, M.J., Vogt, A.P., Hsiao, W. et al. CDX-2 expression in malignant germ cell tumors of the testes, intratubular germ cell neoplasia, and normal seminiferous tubules. Tumor Biol. 33, 2185–2188 (2012). https://doi.org/10.1007/s13277-012-0479-z
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DOI: https://doi.org/10.1007/s13277-012-0479-z