1.     Am J Clin Pathol. 2009 Oct;132(4):531-8.

CDX-2 expression is a common event in primary intestinal-type endocervical adenocarcinoma.

Saad RS, Ismiil N, Dubé V, Nofech-Mozes S, Khalifa MA.

We studied the expression of cytokeratin (CK) 7, CK20, CDX-2, and p16 in 119 cervical adenocarcinomas (65 usual type [50 invasive; 15 in situ], 37 intestinal type [21 invasive; 16 in situ], 10 endometrioid, 5 adenosquamous, and 2 signet-ring carcinomas) in comparison with 55 cases of rectal adenocarcinomas. The percentage of cells staining was considered negative if 0% to 5% stained; more than 5% was considered positive. For p16, staining of more than 50% was considered positive. CK7 was expressed in all cervical cases and in 12 rectal adenocarcinomas (22%). CK20 was expressed in 17 cervical adenocarcinomas (14.3%) and in 48 rectal adenocarcinomas (87%). CK20 immunostaining was diffuse in the majority of rectal tumors but focal in most cervical tumors. CDX-2 was expressed in all cases of rectal adenocarcinoma and in 46 cervical adenocarcinomas (38.7%): usual type, 10 (15%); intestinal type, 31 (84%); endometrioid type, 5 (50%); adenosquamous and signet-ring types, 0 (0%). CDX-2 is a marker for intestinal differentiation irrespective of a rectal or cervical origin. Therefore, it should not be used as the sole basis to confirm the colorectum as the primary origin in metastatic cases.

2.    Appl Immunohistochem Mol Morphol. 2008 Oct;16(5):453-8.

Intestinal type and endocervical-like ovarian mucinous neoplasms are immunophenotypically distinct entities.

Lin X, Lindner JL, Silverman JF, Liu Y.

Ovarian mucinous neoplasm (OMN) is traditionally classified as either intestinal type or endocervical-like subtypes. The 2 subtypes represent different clinicopathologic characteristics. The immunophenotype of the 2 subtypes has not been adequately investigated. In this study, we investigated 14 intestinal type OMNs (borderline and adenocarcinoma) and 12 endocervical-like OMNs (borderline and adenocarcinoma) for their expression of PDX-1, CDX-2, CA-125, CK7, CK20, WT-1, D2-40, and TTF-1. We also included 15 colorectal adenocarcinomas metastatic in the ovary, as they may occasionally mimic OMN. The intestinal type OMNs were positive for PDX-1 (100%), CK7 (100%), CK20 (100%), CDX-2 (29%), whereas were negative for CA-125. The endocervical-like OMNs were positive for CA-125 (100%) and CK7 (100%), whereas were negative for CK20, PDX-1, and CDX-2. Metastatic colorectal adenocarcinomas were positive for CK20 (100%), CDX-2 (100%), and PDX-1 (33%), whereas were negative for CA-125 and CK7. All of the intestinal type and endocervical-like OMNs as well as metastatic colorectal adenocarcinomas were negative for WT-1, D2-40, and TTF-1. Our results demonstrated that the intestinal type and endocervical-like OMNs are immunophenotypically distinct entities. The 2 subtypes can be separated from metastatic colorectal adenocarcinoma by the different immunohistochemical profile of PDX-1, CA-125, CK7, CK20, and CDX-2. In the work-up of mucinous adenocarcinoma in the ovary or abdominal cavity, caution should be exercised in interpreting the possible primary site on the basis of the immunohistochemical profiles.

3.    Int J Gynecol Pathol. 2008 Jan;27(1):92-100.

Intestinal-type cervical adenocarcinoma in situ and adenocarcinoma exhibit a partial enteric immunophenotype with consistent expression of CDX2.

McCluggage WG, Shah R, Connolly LE, McBride HA.

Most cases of cervical adenocarcinoma in situ (AIS) and adenocarcinoma are of the usual or endocervical type. However, intestinal types of AIS and adenocarcinoma exist. With an intestinal-type adenocarcinoma in the cervix, the question may arise as to whether one is dealing with a primary cervical neoplasm or direct or secondary spread from an intestinal adenocarcinoma. In organs such as the ovary, urinary bladder, esophagus, and gallbladder, intestinal-type glandular epithelium often expresses enteric markers, but this has hardly been studied in the cervix. The purpose of this study was to investigate whether intestinal-type AIS and adenocarcinoma in the cervix express enteric markers and to ascertain whether these antibodies are of value in the distinction from a metastatic intestinal adenocarcinoma. We compared the immunophenotype of these lesions with that of usual-type AIS and adenocarcinomain the cervix. Cases included were AIS of usual type (n = 6), primary cervical adenocarcinoma of usual type (n = 6), AIS of intestinal type (n = 21), primary cervical adenocarcinoma of intestinal type (n = 3), primary cervical adenocarcinoma with signet ring cells (n = 2), and colorectal adenocarcinoma involving the cervix (n = 5). All cases were stained with cytokeratin (CK) 7, CK20, monoclonal carcinoembryonic antigen (CEA), p16, and CDX2. Staining was categorized as negative, focally positive (<50% cells), or diffusely positive (50% or more cells). Usual-type AIS was always diffusely CK7 positive, typically diffusely CEA and p16 positive, and always CK20 negative. CDX2 was positive in 1 case. All usual cervical adenocarcinomas were diffusely CK7 and p16 positive, and all were immunoreactive with CEA. Five and 2 cases were CK20 and CDX2 positive, respectively. Intestinal-type AIS was diffusely CK7 positive (all cases) and typically CK20 negative and diffusely CEA and p16 positive. All but 1 case exhibited diffuse nuclear positivity with CDX2. In addition, usual-type AIS adjacent to intestinal type was CDX2 positive in 13 of 21 cases. The 3 cases of primary cervical intestinal-type adenocarcinoma were diffusely CK7 positive, focally or diffusely positive with CK20 and CDX2, and focally positive with CEA. One case was diffusely p16 positive, 1 focal and 1 negative. The foci of signet ring cells in the 2 primary cervical adenocarcinomas were diffusely CK7 and p16 positive and negative with CK20 and CDX2. Colorectal adenocarcinomas involving the cervix were typically diffusely positive with CK20, CEA, and CDX2; negative with CK7; and negative or focally positive with p16. Intestinal types of cervical AIS and adenocarcinoma exhibit a partial enteric immunophenotype, usually with diffuse expression of CDX2 and, in some cases, staining with CK20. They maintain their CK7 immunoreactivity and are usually p16 positive. Although there is immunophenotypic overlap, focal staining with CK20 together with diffuse CK7 and sometimes p16 positivity helps to distinguish intestinal types of cervical adenocarcinoma from involvement by a colorectal adenocarcinoma; CEA and CDX2 are of no value in this regard. CDX2 positivity in usual-type AIS adjacent to intestinal type and in occasional cases of pure usual-type AIS may be a reflection of early intestinal differentiation before this is morphologically apparent. Using a set of cases of AIS diagnosed in a single institution over a 7-year period (77 usual type; 13 intestinal type), intestinal type was more likely to be associated with early invasive adenocarcinoma than usual type (31% vs 17%), suggesting that intestinal differentiation may be a risk factor for invasion in premalignant cervical glandular lesions.

4 .Am J Surg Pathol. 2006 Sep;30(9):1130-9.

Cytokeratins 7 and 20 in primary and secondary mucinous tumors of the ovary: analysis of coordinate immunohistochemical expression profiles and staining distribution in 179 cases.

Vang R, Gown AM, Barry TS, Wheeler DT, Yemelyanova A, Seidman JD, Ronnett BM.

Coordinate expression profiles for cytokeratins 7 and 20 (CK7 and CK20) are useful for distinguishing certain types of adenocarcinomas but use for distinction of primary and secondary mucinous tumors in the ovary is limited due to the existence of a number of tumor types exhibiting overlapping CK7/CK20 immunoprofiles; the use of staining distribution patterns in the distinction of tumors with shared profiles has not been evaluated in detail. We report analysis of both coordinate expression profiles and staining distribution in 179 rigorously classified mucinous tumors in the ovary, including 53 primary tumors [35 atypical proliferative (borderline) mucinous tumors of gastrointestinal type and 18 invasive mucinous carcinomas] and 126 secondary tumors [28 colorectal adenocarcinomas, 54 appendiceal tumors (23 adenocarcinomas, 31 low-grade adenomatous mucinous tumors associated with pseudomyxoma peritonei), 14 pancreatic adenocarcinomas, 8 endocervical adenocarcinomas, 5 gastric adenocarcinomas, 4 gallbladder/biliary tract adenocarcinomas, and 13 adenocarcinomas of unknown primary sites). A CK7+/CK20+ immunoprofile was the most common profile in primary ovarian tumors (74%), upper gastrointestinal tract tumors (78%), and endocervical tumors (88%) but was occasionally observed in lower intestinal tract tumors (colorectal: 11%; appendiceal: 13% of low-grade tumors, 35% of carcinomas). A CK7-/CK20+ immunoprofile was the most common profile in lower intestinal tract tumors (79%) and was uncommon in upper gastrointestinal tract tumors (9%), rarely seen in primary ovarian tumors (4%), and not seen in endocervical tumors. A CK7+/CK20- profile was observed in some primary ovarian (23%), upper gastrointestinal tract (13%), and endocervical tumors (13%) but not in lower intestinal tract tumors. For CK7+ tumors, staining distribution was very frequently diffuse (>50% of tumors cells positive) in primary ovarian, upper gastrointestinal tract, and endocervical tumors, whereas staining distribution was often focal (<50% of tumors cells positive) when present in colorectal and appendiceal carcinomas but not in low-grade appendiceal tumors. For CK20+ tumors, staining distribution was variable but often focal in primary ovarian tumors and nonlower intestinal tract tumors, whereas the pattern was almost always diffuse in lower intestinal tract tumors. Immunohistochemical staining distribution can supplement CK7/CK20 coordinate expression profiles to distinguish subsets of primary ovarian and metastatic lower intestinal tract mucinous tumors having overlapping immunoprofiles but neither coordinate expression profiles nor staining distribution distinguishes primary ovarian tumors from the nonlower intestinal tract metastases.

5. Zhonghua Bing Li Xue Za Zhi. 2001 Apr;30(2):114-7.

[Expression of cytokeratin 7 and 20 in ovarian metastatic carcinomas].

[Article in Chinese]

Dai L, Song Q, Li L, Zhong D, Hui Y.

OBJECTIVE: To study the distinctive clinicopathologic and immunohistochemical difference between ovarian metastatic carcinomas and primary ovarian carcinomas.METHODS: The clinical and pathological features of 27 cases of ovarian metastatic carcinomas (gastric carcinomas 12 cases, colon carcinomas 11 cases, others 4 cases) obtained from our department were reviewed. Immunostainings for CK (AE1/AE3), CK7, CK20, CEA, vimentin, nm23 were performed with SP staining methods.RESULTS: On gross examination, metastasis from gastric adenocarcinoma were usually bilateral, while solid (11/12) and metastases from colonic adenocarcinoma were more often unilateral and cystic (7/11). Microscopically, metastases from gastric adenocarcinoma revealed signet ring cells or poorly differentiated adenocarcinomas (12/12), whereas metastases from colonic adenocarcinomas showed similar morphology of endometrioid adenocarcinoma (8/11). The majority of ovarian metastases of gastric carcinoma (7/12) and colon carcinoma (8/11) were CK20 positive. In particular, CK20 was invariably expressed in colon cancer metastases. Most of the ovarian metastatic carcinomas from the gastrointestinal tract failed to react with immunostaining of CK7. A combined use of CEA, vimentin and nm23 had made a correct classification for 11/12 cases of the gastric carcinoma, 10/11 cases of the colonic cancer.CONCLUSIONS: CK7 and CK20 have been proved to be useful antibodies in distinguishing between metastatic carcinomas and primary carcinomas of the ovary. Combined use of a panel of antibodies can give more significant results