Cytokeratin 7 (CK 7)

Sources/Clones
Accurate (LP5K), American Research Products (RCK105), Biodesign, Biogenesis (C35, C18), Biogenex (OV-TL 12/30), Bioprobe (C-35, C68), Boehringer Mannheim (KS7-18), Chemicon, Dako (OV-TL 12/30), Cymbus Bioscience (C46, LP5K), Dako (OV-TL 12/30), Intracell Corp (RCK105), Japan Tanner (C35, C68), Milab (RCK 105), Novocastra (LP5K), Sanbio (OVTL 12/30, RCK105), Saxon (RCB105), Seralab (CK7) and Sigma (LD5 68).

Fixation/Preparation
Cytokeratin 7 (CK 7) can be used on formalin-fixed, paraffin-embedded tissue sections. Enzymatic digestion with proteolytic enzymes such as trypsin should be performed before staining. Pronase digestion has been found to be harsh on CK 7. This antibody may also be used on acetone-and/or methanol-fixed cryostat sections or fixed-cell smears. It enjoys the additional advantage of being used on cytological preparations already stained by the Papanicolaou stain. For cell smears, the APAAP technique is recommended.

Background
CK 7 antibody reacts with the 54 kD cytokeratin intermediate filament protein isolated from human OTN II ovarian carcinoma cells and other cell lines. Identified as CK 7 according to Moll's catalog, it is a basic cytokeratin found in most glandular and transitional epithelia (Moll et al, 1982).
In normal tissue CK 7 reacts with many ductal and glandular epithelia, but not stratified squamous epithelia. It is also reactive with transitional epithelium of urinary tract. Hepatocytes are negative whilst bile ducts are positive. In addition, lung and breast epithelia are positive with this antibody, whilst colon and prostate epithelial cells are negative (Van Niekerk et al, 1991).

Applications
CK is expressed in specific subtypes of ovarian, breast and lung adenocarcinoma, whilst carcinomas of the colon are negative (Ramackers et al, 1990). Recent studies have indicated that a CK 7+CK 20immunophenotype is helpful in distinguishing metastatic colonic adenocarcinoma from primary ovarian carcinomas, particularly the endometrioid type (and with the exception of the mucinous type) (Loy et al, 1996) (Appendices 1.13, 1.28). Occasional ovarian mucinous carcinomas may show the same immunophenotype as metastatic colonic carcinomas (CK 7-/CK 20+). Using the same immunophenotypic profile (together with CK 18), CK 7 was recently shown to assist in determining that most ovarian mucinous tumors in pseudomyxoma peritonei in woman are secondary to appendiceal adenoma (Ronnett et al, 1997).
CK 7 is also useful to distinguish transitional cell carcinomas (+ve) from prostate cancer (-ve). The failure of CK 7 to interact with squamous cell carcinomas presents the potential for specificity for adenocarcinoma and transitional cell carcinoma.

Comments
We have found the combination of CK 7 and CK 20 to be extremely useful in distinguishing ovarian carcinomas (except mucinous) from colonic adenocarcinomas. Serous ovarian carcinoma tissue is recommended for positive control tissue.

References
•Loy TS, Calaluce RD, Keeney GL 1996. Cytokeratin immunostaining in differentiating primary ovarian carcinoma from metastatic colonic adenocarcinoma. Modern Pathology 9: 1040,-1044.

•Moll R, Franke WW, Schiller DL, Geiger B, Krepler R 1982. The catalog of human cytokeratins: patterns of expression in normal epithelia, tumors and cultured cells. Cell 31: 11-24.

•Ramackers F, Van Niekerk C, Poels L et al 1990. Use of monoclonal antibodies to keratin 7 in differential diagnosis of adenocarcinomas. American Journal of Pathology 136: 641-655.

•Ronnett BM, Shmookler BM, Diener-West M, Sugarbaker PH, Kurman RJ 1997. Immunohistochemical evidence supporting the appendiceal origin of pseudomyxoma peritonei in women. International Journal of Gynecologic Pathology 16: 1-9.

•Van Niekerk CC, Jap PHK, Raemaekers FCS, Van De Molengraft F, Poels LG 1991. Immunohistochemical demonstration of keratin 7 in routinely fixed paraffin embedded tissues. Journal of Pathology 165: 145-152.

Bibliografía
Manual of diagnostic antibodies for immunohistology / Anthony S.-Y. Leong, Kumarasen Cooper, F. Joel W.-M. Leong.