CDX-2 Homeobox Gene Expression Is a Reliable Marker of Colorectal Adenocarcinoma Metastases to the Lungs

Department of Pathology, Santa Chiara Hospital, Trento, Italy.
American Journal of Surgical Pathology (Impact Factor: 5.15). 03/2003; 27(2):141-9. DOI: 10.1097/00000478-200302000-00001
Source: PubMed


Lung metastases from colorectal carcinomas (CRC) can be resected with improved survival. The distinction between primary lung adenocarcinomas and metastases from CRC may sometimes be difficult, especially on cytologic specimens or small bronchoscopic biopsies. Immunohistochemistry may be of help in this setting: available markers include TTF-1 and SP-A, which are markers of lung origin, whereas there are no good markers of intestinal origin, besides cytokeratin 7 and 20 coexpression pattern, which is not very specific. The nuclear CDX-2 transcription factor, which is the product of a homeobox gene necessary for intestinal organogenesis, is expressed in normal colonic epithelia and most colorectal adenocarcinomas, and could potentially be of diagnostic usefulness. Our aim was to investigate CDX-2 immunohistochemical expression using a new monoclonal antibody and to verify if CDX-2 can be a reliable marker to identify the colorectal origin of lung metastases. CDX-2 expression was evaluated in formalin-fixed, paraffin-embedded samples of normal adult human tissues (50 samples) and in 299 surgically resected carcinomas of different origins, including 125 non-lung adenocarcinomas, 117 primary lung tumors, 5 mesotheliomas, and 52 adenocarcinomas metastatic to the lung. CDX-2 was also evaluated on a series of 20 bioptic and 10 cytologic specimens (5 cases of colorectal metastases to the lung, 5 cases of metastases from other organs, and 10 primary lung adenocarcinomas). In normal tissues CDX-2 immunoreactivity was observed only in ileal and colorectal epithelia. CDX-2 was expressed in almost all primary and metastatic CRC (88 of 90) and was never observed in primary lung tumors. CDX-2 was also expressed in a limited group of adenocarcinomas of other sites (gastric, biliopancreatic, and mucinous ovarian adenocarcinomas). CDX-2 could be easily detected in all bioptic and cytologic samples of CRC metastases. CDX-2 is a reliable, specific, and sensitive immunohistochemical marker of normal and neoplastic intestinal epithelium. CDX-2 can be easily applied to routine histologic and cytologic material and is therefore a useful marker in the differential diagnosis of primary versus metastatic adenocarcinomas in the lung, and among metastases from an unknown primary, supports intestinal origin.

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    • "Therefore, the CK20+/CK7- phenotype indicates metastatic adenocarcinoma, most often from the colorectum. In regard to CDX2, Barbareschi et al. showed that CDX2 immunostained all colorectal adenocarcinomas metastatic to the lung, although it was completely absent in all primary lung neoplasm and in all other adenocarcinoma metastatic to the lung [12]. However, CDX2 is not entirely specific for colorectal cancer, because Weling RW et al. reported that the expression of CDX2 was found ovarian mucinous carcinoma, adenocarcinoma of the urinary bladder, and prostatic adenocarcinoma [13]. "
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    ABSTRACT: Background Urethral metastatic adenocarcinoma is extremely rare. Moreover, only 9 previous cases with metastases from colorectal cancer have been reported to date, and not much information on urethral metastases from colorectum is available so far. Case presentation We report our experience in the diagnosis and the management of the case with urethral metastasis from a sigmoid colon cancer. A 68-year-old man, who underwent laparoscopic sigmoidectomy for sigmoid colon carcinoma four years ago, presented gross hematuria with pain. Urethroscopy identified a papillo-nodular tumor 7 mm in diameter in the bulbar urethra. CT-scan imaging revealed the small mass of bulbous portion of urethra and solitary lung metastasis. Histological examination of the tumor obtained by transurethral resection showed moderately differentiated adenocarcinoma, which was diagnosed as a metastasis of a sigmoid colon carcinoma pathologically by morphological examination. Immunohistochemical analysis of the urethral tumor revealed the positive for cytokertin 20 and CDX2, whereas negative for cytokertin 7. These features were consistent with metastatic adenocarcinoma of the sigmoid colon cancer. As the management of this case with urethral and lung metastasis, 6-cycle of chemotherapy with fluorouracil with leucovorin plus oxaliplatin was administered to the patient, and these metastases were disappeared with no recurrence of disease for 34 months. Conclusion Urethral metastasis from colorectal cancer is a very rare occurrence. However, in the presence of urinary symptoms, the possibility of the urethral metastasis should be considered.
    BMC Surgery 05/2014; 14(1):31. DOI:10.1186/1471-2482-14-31 · 1.40 Impact Factor
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    • "Using tissue microarrays, Moskaluk et al [29] analyzed CDX2 staining in 745 samples of human cancer and arrived at similar conclusions. Barbareschi et al [30] compared CDX2 expression in primary and metastatic tumors found in the lung and concluded that this marker is highly selective for tumors originating from the colon and rectum, but also stains metastases from the stomach and ovary. In our study, CDX2 was expressed in 114 of 118 (97%) colorectal, 36 of 59 (61%) gastric, and 5 of 32(16%) pancreatic adenocarcinomas. "
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    ABSTRACT: Metastatic adenocarcinoma from an unknown primary site is a common clinical problem. Determining the cytokeratin (CK) 7/CK20 pattern of tumors is one of the most helpful procedures for this purpose since the CK7-/CK20+ pattern is typical of colorectal adenocarcinomas. CDX2, a critical nuclear transcription factor for intestinal development, is expressed in intestinal epithelium and adenocarcinomas. In the present study, we compared the sensitivity and specificity of CDX2 expression and the CK7-/CK20+ phenotype in differentiating colorectal adenocarcinomas from pancreatic and gastric adenocarcinomas. CK7/CK20 staining pattern and CDX2 expression were evaluated in 118 cases of colorectal, 59 cases of gastric, and 32 cases of pancreatic adenocarcinomas. The sensitivity, specificity, and positive and negative predictive values of the CK7-/CK20+ phenotype and of CDX2 expression were analyzed. The CK7-/CK20+ immunophenotype was expressed by 75 of 118 (64%) colorectal and 3 of 59 (5%) gastric tumors and was not observed in any pancreatic adenocarcinomas. The CK7+/CK20+ immunophenotype was expressed in 24/118 (20%) of colon, 28/59 (48%) of gastric and 7/32 (22%) of pancreatic adenocarcinomas. The CK7+/CK20- expression pattern was observed in only 2% (2 of 118) of colorectal carcinomas. CDX2 was expressed in 114 of 118 (97%) colorectal, 36 of 59 (61%) gastric, and 5 of 32(16%) pancreatic adenocarcinomas. There was no significant association between CDX2 expression and tumor differentiation in colorectal carcinomas. In gastric carcinomas, CDX2 expression was more common in intestinal type tumors than in diffuse type carcinomas. The CK7-/CK20+ phenotype showed a specificity of 96.7% in predicting colorectal adenocarcinomas, which was superior to that of CDX2 expression. CDX2 expression at both cut-off levels (> 5% and > 50%) had a higher sensitivity (96.6% and 78%) than the CK phenotype. Both the CK7-/CK20+ phenotype and expression of the antibody CDX2 are highly specific and sensitive markers of colorectal origin. CDX2 expression should be a useful adjunct for the diagnosis of intestinal adenocarcinomas, particularly when better established markers such as CK7 and CK20 yield equivocal results. The CK7-/CK20+ phenotype is superior in its specificity and positive predictive value and might be preferred. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here:
    Diagnostic Pathology 01/2012; 7(1, article 9):9. DOI:10.1186/1746-1596-7-9 · 2.60 Impact Factor
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    • "commonly used to search for an unknown primary adenocarcinoma [24]. CDX-2 positivity is a very reliable marker for intestinal differentiation , showing a positivity of 100% in the present study and ranging from 72% to 100% in other series [1] [9] [29]. On the other hand, it should be emphasized that there can be aberrant expression in primary large cell carcinomas, as well as in adenocarcinomas and bronchioloalveolar carcinomas of the lung, mimicking CRC [19] [26]. "
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    ABSTRACT: Although thyroid transcription factor-1 (TTF-1) immunoreactivity is considered as a specific marker of lung and thyroid neoplasms, it may be positive in a proportion of extrapulmonary adenocarcinomas. This study examined the expression of TTF-1 in 555 colorectal adenocarcinomas using three commercial monoclonal antibodies: clone SPT24 (Novocastra) and 8G7G3/1 (Dako and Cell Marque), and compared the TTF-1 staining with other immunohistochemical markers, cytokeratin (CK) 7, CK 20, caudal-type homeobox transcription factor 2 (CDX2), and MUC2. The clinicopathological prognostic factors were compared with the TTF-1 expression status. Nuclear TTF-1 staining was detected in 24 cases (4.3%) with the SPT24 antibody and 18 cases (3.2%) with the 8G7G3/1 antibody. All cases positive for 8G7G3/1 were also positive for SPT24. CDX2 was expressed constantly in all 24 TTF-1-positive colorectal cancers, whereas CK7, CK20, and MUC2 were detected in 2 (8.3%), 23 (95.8%), and 8 (33.3%) cases, respectively. There was no correlation between TTF-1 expression and clinicopathological significance. To avoid potential pitfalls, TTF-1 should be interpreted in conjunction with the clinical setting, histological features, and the results of other markers, such as CK7, CK20, and CDX2. MUC2 can be used as supplementary information to confirm difficult cases.
    Pathology - Research and Practice 11/2011; 207(11):686-90. DOI:10.1016/j.prp.2011.08.009 · 1.40 Impact Factor
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