Indian Journal of Pathology and Microbiology
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Year : 2011  |  Volume : 54  |  Issue : 4  |  Page : 860-861
Aberrant CDX2 expression and metastatic endometrial adenocarcinoma to the lung

Unit of Pathologic Anatomy and Oncology, A.O. "San Giovanni di Dio e Ruggi d'Aragona" via S., Leonardo, Salerno, Italy

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Date of Web Publication6-Jan-2012

How to cite this article:
D'Antonio A. Aberrant CDX2 expression and metastatic endometrial adenocarcinoma to the lung. Indian J Pathol Microbiol 2011;54:860-1

How to cite this URL:
D'Antonio A. Aberrant CDX2 expression and metastatic endometrial adenocarcinoma to the lung. Indian J Pathol Microbiol [serial online] 2011 [cited 2022 Jan 18];54:860-1. Available from: https://www.ijpmonline.org/text.asp?2011/54/4/860/91536


We read with great interest the report "CDX2 positivity in metastatic endometrial carcinoma to the lung: A diagnostic pitfall" by Deodhar et al.[1] that described a case of metastatic endometrial adenocarcinoma to the lung with aberrant expression of CDX2. I think this article raised some interesting points particularly regarding the role of CDX2 and the differential diagnosis of pulmonary mass in patients without a previous history of primary tumor in other sites. CDX2 is a homeobox gene that has been shown to play a role in the development of the small and large intestine in mammals and in the differentiation of intestinal epithelial cells. Different reports, using tissue microarrays containing most normal tissue types and an antibody to the CDX2 protein, have demonstrated a strong diffuse CDX2 staining only in the nuclei of small and large intestinal epithelium and portions of the pancreatic duct system. [2] Furthermore, CDX2 has been identified as a marker of colon cancer (>90% of cases) and less frequently (20-30% of cases) showed extensive staining in adenocarcinomas of the stomach, esophagus, and ovary (endometrioid and mucinous types). [2] In other reports, the CDX2 expression has been documented also in adenocarcinomas of the pancreas, gallbladder and urinary bladder, and this expression has been interpreted as intestinal differentiation. Conversely, Wani et al. [3] have described an aberrant expression of CDX2 in the female genital tract (uterus and ovary) in association with the presence of morular differentiation in adenocarcinoma and polyps such as in variable number of morule-forming tumors of other sites as pyloric gland type adenoma of stomach and gallbladder. These data suggested that the presence of aberrant expression of CDX2 was not exclusively correlated to intestinal differentiation but also with presence of morular/squamous changes within different tumors. In these cases, CDX2 expression appeared to correlate closely to nuclear accumulation of β-catenin and resulted associated with a variable degree of cytoplasmic positivity. [3] This feature is not surprising; in fact, nuclear beta-catenin is required for changes in morphology from glandular to morular phenotypes of endometrial carcinoma. Various studies have demonstrated previously that the homeodomain transcription factor CDX2 increases markedly during intestinal epithelial cell differentiation. Saegusa et al. have suggested that over-expression of CDX2 mediated by nuclear beta-catenin and CDX2 itself can cause an inhibition of epithelial cells proliferation of endometrial adenocarcinoma through up-regulation of p21(Waf1) expression, modulating beta-catenin-mediated transcription and indicated the association between CDX2 and beta-catenin signaling as responsible of the induction of trans-differentiation of carcinoma cells. [4] In addition, had been described a loss of CDX2 expression in dedifferentiated tumors with an increment of nuclear expression of beta-catenin. Strikingly, this is reversed in growing metastases, indicating an active role of CDX2 and beta-catenin also in malignant tumor progression and metastatic disease. [4] These data could be cause of subsequent studies in most large series of tumors in different organs. Finally, I agree with the suggestion of the authors on the practical implication and the risk of a diagnostic pitfall of an aberrant expression of CDX2 particularly on the small biopsy and in the cases which a squamous differentiation is not apparent. I would like to comment that I have experienced personally the difficult of differential diagnosis of the extra-gastrointestinal tumors with CDX2 positivity in daily routine histopathologic findings. In fact, I have independently observed some cases of primary and metastatic adenocarcinoma intestinal-type arising in different organs that expressed nuclear CDX2. [5] These cases comprised also two mucinous-type pulmonary adenocarcinomas and one case of mesotelioma with glandular differentiation. Moreover, in patient with metastatic foci of colorectal adenocarcinoma without a previous diagnosis of primary tumor the role of CDX2 in the differential diagnosis remain relevant because it is a sensitive although not specific marker of an intestinal origin of neoplasia. The pathologist should keep in the mind the possibility that adenocarcinoma of different origin with or without morular differentiation can express CDX2. In these cases, a little panel of antibodies including CK7 and CK20 may be useful to exclude a colorectal adenocarcinoma. A careful evaluation of clinical history, some morphologic features (like as the presence of intraglandular necrosis in colorectal adenocarcinoma), CK7 positivity, and negative staining for CK20 may to help for the correct diagnosis.

   References Top

1.Deodhar KK, Gupta S, Karimundackal G, Tongaonkar HB. CDX2 positivity in metastatic endometrial carcinoma to the lung: A diagnostic pitfall. Indian J Pathol Microbiol 2011;54:858-60   Back to cited text no. 1
2.Moskaluk CA, Zhang H, Powel SM, Cerilli LA, Hampton GM, Frierson Jr HF. CDX2 Protein Expression in Normal and Malignant Human Tissues: An Immunohistochemical Survey Using Tissue Microarrays. Mod Pathol 2003;16:913-9.  Back to cited text no. 2
3.Wani Y, Notohara K, Nakatani Y, Matsuzaki A. Aberrant nuclear CDX2 expression in morule-forming tumours in different organs, accompanied by cytoplasmic reactivity. Histopathology 2009;55:465-8.  Back to cited text no. 3
4.Saegusa M, Hashimura M, Kuwata T, Hamano M, Wani Y, Okayasu I. A functional role of CDX2 in beta-catenin signaling during transdifferentiation in endometrial carcinomas. Carcinogenesis 2007;28:1885-92.  Back to cited text no. 4
5.D'Antonio A, Addesso M, De Dominicis G, Boscaino A, Liguori G, Nappi O. Mucinous carcinoma of thyroid gland. Report of a primary and a metastatic mucinous tumour from ovarian adenocarcinoma with immunohistochemical study and review of literature. Virchows Arch 2007;451:847-51.  Back to cited text no. 5

Correspondence Address:
Antonio D'Antonio
Unit of Pathologic Anatomy, A.O. "San Giovanni di Dio e Ruggi d'Aragona" via S. Leonardo, Salerno
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.91536

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