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Published in: BMC Clinical Pathology 1/2006

Open Access 01-12-2006 | Research article

Inclusion of MUC1 (Ma695) in a panel of immunohistochemical markers is useful for distinguishing between endocervical and endometrial mucinous adenocarcinoma*

Authors: Thaer Khoury, Dongfeng Tan, Jianmin Wang, Marilyn Intengan, Jun Yang, Sadir Alrawi, Peisha Yan, James C Byrd

Published in: BMC Clinical Pathology | Issue 1/2006

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Abstract

Background

Distinguishing endocervical adenocarcinoma (ECA) from endometrial mucinous adenocarcinoma (EMMA) is clinically significant in view of the differences in their management and prognosis. In this study, we used a panel of tumor markers to determine their ability to distinguish between primary endocervical adenocarcinoma and primary endometrial mucinous adenocarcinoma.

Methods

Immunohistochemistry using monoclonal antibodies to MUC1 (Ma695), p16, estrogen receptor (ER), progesterone receptor (PR), and vimentin, was performed to examine 32 cases, including 18 EMMAs and 14 ECAs. For MUC1, cases were scored based on the percentage of staining pattern, apical, apical and cytoplasmic (A/C), or negative. For p16, cases were scored based on the percentage of cells stained. For the rest of the antibodies, semiquantitative scoring system was carried out.

Results

For MUC1, majority of EMMA (14 of 18 cases, 78%) showed A/C staining, whereas only few ECA (2 of 14, 14%) were positive. The difference of MUC1 expression in the two groups of malignancy was statistically significant (p < 0.001). Staining for p16 was positive in 10 of 14 (71%) ECA and 4 of 18 (22%) EMMA. Estrogen receptor was positive in 3 of 14 (21%) ECA and 17 of 18 (94%) EMMA. Progesterone receptor was positive in 3 of 14 (21%) ECA and 16 of 18 (89%) EMMA. Vimentin was positive in 1 of 14 (7%) ECA, and 9 of 18 (50%) EMA, with median and range of 0 (0–6), and 1.5 (0–9) respectively.

Conclusion

A panel of immunohistochemical markers including MUC1, p16, ER, PR, and vimentin is recommended, when there is morphological and clinical doubt as to the primary site of endocervical or endometrial origin.
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Literature
1.
go back to reference Berek JS, Hacker NV: cervical cancer, and uterine cancer. Practical Gynecologic Oncology. Edited by: Lippincott Williams, Wilkins. 2000, Philadelphia, 354: 421-3 Berek JS, Hacker NV: cervical cancer, and uterine cancer. Practical Gynecologic Oncology. Edited by: Lippincott Williams, Wilkins. 2000, Philadelphia, 354: 421-3
2.
go back to reference Hoskins WJ, Perez CA, Young RC: uterine cervix, and corpus: epithelial tumors. Principles and Practice of Gynecologic Oncology. Edited by: Lippincott JB. 2005, Philadelphia, 763: 843-4 Hoskins WJ, Perez CA, Young RC: uterine cervix, and corpus: epithelial tumors. Principles and Practice of Gynecologic Oncology. Edited by: Lippincott JB. 2005, Philadelphia, 763: 843-4
3.
go back to reference Kamoi S, AlJuboury MI, Akin M, Silverberg SG: Immunohistochemical staining in the distinction between primary endometrial and endocervical adenocarcinomas: Another viewpoint. Int J Gyn Pathol. 2002, 21: 217-223. 10.1097/00004347-200207000-00003.CrossRef Kamoi S, AlJuboury MI, Akin M, Silverberg SG: Immunohistochemical staining in the distinction between primary endometrial and endocervical adenocarcinomas: Another viewpoint. Int J Gyn Pathol. 2002, 21: 217-223. 10.1097/00004347-200207000-00003.CrossRef
4.
go back to reference McCluggage WG, Sumathi VP, McBride HA, Patterson A: A panel of immunohistochemical stains including carcinoembryonic antigen, vimentin, and estrogen receptor aids in the distinction between primary endometrial and endocervical adenocarcinomas. Int J Gynecol Pathol. 2002, 21: 11-5. 10.1097/00004347-200201000-00003.CrossRefPubMed McCluggage WG, Sumathi VP, McBride HA, Patterson A: A panel of immunohistochemical stains including carcinoembryonic antigen, vimentin, and estrogen receptor aids in the distinction between primary endometrial and endocervical adenocarcinomas. Int J Gynecol Pathol. 2002, 21: 11-5. 10.1097/00004347-200201000-00003.CrossRefPubMed
5.
go back to reference Zaino RJ: The fruits of our labors: distinguishing endometrial from endocervical adenocarcinoma. Int J Gynecol Pathol. 2002, 21: 1-3. 10.1097/00004347-200201000-00001.CrossRefPubMed Zaino RJ: The fruits of our labors: distinguishing endometrial from endocervical adenocarcinoma. Int J Gynecol Pathol. 2002, 21: 1-3. 10.1097/00004347-200201000-00001.CrossRefPubMed
6.
go back to reference Wahlstrom T, Lindgren J, Korhonen M, Seppala M: Distinction between endocervical and endometrial adenocarcinoma with immunoperoxidase staining of carcinoembryonic antigen in routine histological specimens. Lancet. 1979, 2: 1159-61. 10.1016/S0140-6736(79)92386-9.CrossRefPubMed Wahlstrom T, Lindgren J, Korhonen M, Seppala M: Distinction between endocervical and endometrial adenocarcinoma with immunoperoxidase staining of carcinoembryonic antigen in routine histological specimens. Lancet. 1979, 2: 1159-61. 10.1016/S0140-6736(79)92386-9.CrossRefPubMed
7.
go back to reference Cohen C, Shulman G, Budgeon L: Endocervical and endometrial adenocarcinoma: an immunoperoxidase and immunohistochemical study. Am J Surg Pathol. 1982, 6: 151-7.CrossRefPubMed Cohen C, Shulman G, Budgeon L: Endocervical and endometrial adenocarcinoma: an immunoperoxidase and immunohistochemical study. Am J Surg Pathol. 1982, 6: 151-7.CrossRefPubMed
8.
go back to reference Dabbs DJ, Geisinger KR, Norris HT: Intermediate filaments in endometrial and endocervical carcinomas. The diagnostic utility of vimentin patterns. Am J Surg Pathol. 1986, 10: 568-76.CrossRefPubMed Dabbs DJ, Geisinger KR, Norris HT: Intermediate filaments in endometrial and endocervical carcinomas. The diagnostic utility of vimentin patterns. Am J Surg Pathol. 1986, 10: 568-76.CrossRefPubMed
9.
go back to reference Dabbs D, Geisinger K: Selective applications of immunohistochemistry in gynecological neoplasms. Pathol Annu. 1993, 28 (1): 329-53.PubMed Dabbs D, Geisinger K: Selective applications of immunohistochemistry in gynecological neoplasms. Pathol Annu. 1993, 28 (1): 329-53.PubMed
10.
go back to reference Dabbs D, Sturtz K, Zaino R: The immunohistochemical discrimination of endometrioid adenocarcinomas. Hum Pathol. 1996, 27: 172-7. 10.1016/S0046-8177(96)90371-8.CrossRefPubMed Dabbs D, Sturtz K, Zaino R: The immunohistochemical discrimination of endometrioid adenocarcinomas. Hum Pathol. 1996, 27: 172-7. 10.1016/S0046-8177(96)90371-8.CrossRefPubMed
11.
go back to reference Toda T, Sadi AM, Egawa H, Atari E, Qureshi B, Nagai Y: Affinity of four lectins for endocervical and endometrial non-neoplastic and neoplastic glandular epithelium. Histopathology. 1998, 32: 257-63. 10.1046/j.1365-2559.1998.00346.x.CrossRefPubMed Toda T, Sadi AM, Egawa H, Atari E, Qureshi B, Nagai Y: Affinity of four lectins for endocervical and endometrial non-neoplastic and neoplastic glandular epithelium. Histopathology. 1998, 32: 257-63. 10.1046/j.1365-2559.1998.00346.x.CrossRefPubMed
12.
go back to reference Staebler A, Sherman ME, Ronnett BM: Hormone receptor immunohistochemistry (IHC) and HPV in situ hybridization (ISH) are useful for distinguishing between primary endocervical and endometrial adenocarcinomas. Mod Pathol. 2001, 14: 856- Staebler A, Sherman ME, Ronnett BM: Hormone receptor immunohistochemistry (IHC) and HPV in situ hybridization (ISH) are useful for distinguishing between primary endocervical and endometrial adenocarcinomas. Mod Pathol. 2001, 14: 856-
13.
go back to reference Castrillon D, Lee K, Nucci M: Distinction between endometrial and endocervical adenocarcinoma: an immunohistochemical study. Int J Gynecol Pathol. 2002, 21: 4-10. 10.1097/00004347-200201000-00002.CrossRefPubMed Castrillon D, Lee K, Nucci M: Distinction between endometrial and endocervical adenocarcinoma: an immunohistochemical study. Int J Gynecol Pathol. 2002, 21: 4-10. 10.1097/00004347-200201000-00002.CrossRefPubMed
14.
go back to reference Maes G, Fleuren GJ, Bara J, Nap M: The distinction of mucins, carcinoembryonic antigen, and mucus-associated antigens in endocervical and endometrial adenocarcinomas. Int J Gynecol Pathol. 1988, 7: 112-22.CrossRefPubMed Maes G, Fleuren GJ, Bara J, Nap M: The distinction of mucins, carcinoembryonic antigen, and mucus-associated antigens in endocervical and endometrial adenocarcinomas. Int J Gynecol Pathol. 1988, 7: 112-22.CrossRefPubMed
15.
go back to reference Kudo R, Sasano H, Koizumi M, Orenstein JM, Silverberg SG: Immunohistochemical comparison of new monoclonal antibody 1C5 and carcinoembryonic antigen in the differential diagnosis of adenocarcinoma of the uterine cervix. Int J Gynecol Pathol. 1990, 9: 325-36.CrossRefPubMed Kudo R, Sasano H, Koizumi M, Orenstein JM, Silverberg SG: Immunohistochemical comparison of new monoclonal antibody 1C5 and carcinoembryonic antigen in the differential diagnosis of adenocarcinoma of the uterine cervix. Int J Gynecol Pathol. 1990, 9: 325-36.CrossRefPubMed
16.
go back to reference McCluggage WG, Jenkins D: p16 immunoreactivity may assist in the distinction between endometrial and endocervical adenocarcinoma. Int J Gynecol Pathol. 2003, 22 (3): 231-235. 10.1097/01.PGP.0000055172.04957.2F.CrossRefPubMed McCluggage WG, Jenkins D: p16 immunoreactivity may assist in the distinction between endometrial and endocervical adenocarcinoma. Int J Gynecol Pathol. 2003, 22 (3): 231-235. 10.1097/01.PGP.0000055172.04957.2F.CrossRefPubMed
17.
go back to reference Ansari-Lari MA, Staebler A, Zaino RJ, Shah KV, Ronnett BM: Distinction of endocervical and endometrial adenocarcinomas: immunohistochemical p16 expression correlated with human papillomavirus (HPV) DNA detection. Am J Surg Pathol. 2004, 28 (2): 160-167.CrossRefPubMed Ansari-Lari MA, Staebler A, Zaino RJ, Shah KV, Ronnett BM: Distinction of endocervical and endometrial adenocarcinomas: immunohistochemical p16 expression correlated with human papillomavirus (HPV) DNA detection. Am J Surg Pathol. 2004, 28 (2): 160-167.CrossRefPubMed
18.
go back to reference Dekker J, Rossen JW, Buller HA: The MUC family: an obituary. Trends Biochem Sci. 2002, 27: 126-131. 10.1016/S0968-0004(01)02052-7.CrossRefPubMed Dekker J, Rossen JW, Buller HA: The MUC family: an obituary. Trends Biochem Sci. 2002, 27: 126-131. 10.1016/S0968-0004(01)02052-7.CrossRefPubMed
19.
go back to reference Oniaux N, Escande F, Porchet N: Structural organization and classification of the human mucin genes. Front Biosci. 2001, 6: 1192-1206.CrossRef Oniaux N, Escande F, Porchet N: Structural organization and classification of the human mucin genes. Front Biosci. 2001, 6: 1192-1206.CrossRef
20.
go back to reference Brayman M, Thathiah A, Carson DD: MUC1: a multifunctional cell surface component of reproductive tissue epithelia. Reprod Biol Endocrinol. 2004, 2: 4-10.1186/1477-7827-2-4.CrossRefPubMedPubMedCentral Brayman M, Thathiah A, Carson DD: MUC1: a multifunctional cell surface component of reproductive tissue epithelia. Reprod Biol Endocrinol. 2004, 2: 4-10.1186/1477-7827-2-4.CrossRefPubMedPubMedCentral
21.
go back to reference Langner C, Ratschek M, Rehak P, Schips L, Zigeuner R: Expression ofMUC1 (EMA) and E-cadherin in renal cell carcinoma: a systematic immunohistochemical analysis of 188 cases. Mod Pathol. 2004, 17: 180-8. 10.1038/modpathol.3800032.CrossRefPubMed Langner C, Ratschek M, Rehak P, Schips L, Zigeuner R: Expression ofMUC1 (EMA) and E-cadherin in renal cell carcinoma: a systematic immunohistochemical analysis of 188 cases. Mod Pathol. 2004, 17: 180-8. 10.1038/modpathol.3800032.CrossRefPubMed
22.
go back to reference Sivridis E, Giatromanolaki A, Koukourakis MI, Georgiou L, Anastasiadis P: Patterns of episialin/MUC1 expression in endometrial carcinomas and prognostic relevance. Histopathology. 2002, 40: 92-100. 10.1046/j.1365-2559.2002.01316.x.CrossRefPubMed Sivridis E, Giatromanolaki A, Koukourakis MI, Georgiou L, Anastasiadis P: Patterns of episialin/MUC1 expression in endometrial carcinomas and prognostic relevance. Histopathology. 2002, 40: 92-100. 10.1046/j.1365-2559.2002.01316.x.CrossRefPubMed
23.
go back to reference Acosta AA, Elberger L, Borghi M: Endometrial dating and determination of the window of implantation in healthy fertile women. Fertility & Sterility. 2000, 73: 788-98. 10.1016/S0015-0282(99)00605-6.CrossRef Acosta AA, Elberger L, Borghi M: Endometrial dating and determination of the window of implantation in healthy fertile women. Fertility & Sterility. 2000, 73: 788-98. 10.1016/S0015-0282(99)00605-6.CrossRef
24.
go back to reference Carson DD, DeSouza MM, Kardon R, Zhao X, Lagow E, Julian J: Mucin expression and function in the female reproductive tract. Human Reproduction Update. 1998, 4: 459-464. 10.1093/humupd/4.5.459.CrossRefPubMed Carson DD, DeSouza MM, Kardon R, Zhao X, Lagow E, Julian J: Mucin expression and function in the female reproductive tract. Human Reproduction Update. 1998, 4: 459-464. 10.1093/humupd/4.5.459.CrossRefPubMed
25.
go back to reference Meseguer M, Pellicer A, Simon C: MUC1 and endometrial receptivity. Molecular Human Reproduction. 1998, 4: 1089-98. 10.1093/molehr/4.12.1089.CrossRefPubMed Meseguer M, Pellicer A, Simon C: MUC1 and endometrial receptivity. Molecular Human Reproduction. 1998, 4: 1089-98. 10.1093/molehr/4.12.1089.CrossRefPubMed
26.
go back to reference Meseguer M, Aplin JD: Human endometrial mucin MUC1 is up-regulated by progesterone and down-regulated in vitro by the human blastocyst. Biology of Reproduction. 2001, 64: 590-601. 10.1095/biolreprod64.2.590.CrossRefPubMed Meseguer M, Aplin JD: Human endometrial mucin MUC1 is up-regulated by progesterone and down-regulated in vitro by the human blastocyst. Biology of Reproduction. 2001, 64: 590-601. 10.1095/biolreprod64.2.590.CrossRefPubMed
27.
go back to reference Gipson IK: Mucin genes expressed by human female reproductive tractepithelia. Biology of Reproduction. 1997, 56: 999-1011. 10.1095/biolreprod56.4.999.CrossRefPubMed Gipson IK: Mucin genes expressed by human female reproductive tractepithelia. Biology of Reproduction. 1997, 56: 999-1011. 10.1095/biolreprod56.4.999.CrossRefPubMed
28.
go back to reference Hewetson A, Chilton BS: Molecular cloning and hormone-dependent expression of rabbit Muc1 in the cervix and uterus. Biol Reprod. 1997, 57: 468-77. 10.1095/biolreprod57.2.468.CrossRefPubMed Hewetson A, Chilton BS: Molecular cloning and hormone-dependent expression of rabbit Muc1 in the cervix and uterus. Biol Reprod. 1997, 57: 468-77. 10.1095/biolreprod57.2.468.CrossRefPubMed
29.
go back to reference Price MR, Rye PD, Petrakou E: Summary report on the ISOBM TD-4 Workshop: analysis of 56 monoclonal antibodies against the MUC1 mucin. Tumor Biol. 1998, 19 (Suppl 1): 1-20. 10.1159/000056500.CrossRef Price MR, Rye PD, Petrakou E: Summary report on the ISOBM TD-4 Workshop: analysis of 56 monoclonal antibodies against the MUC1 mucin. Tumor Biol. 1998, 19 (Suppl 1): 1-20. 10.1159/000056500.CrossRef
30.
go back to reference Remmele W, Schicketanz K-H: Immunohistochemical determination of estrogen and progesterone receptor content in human breast cancer. Computer-assisted image analysis (QIC score) vs. subjective grading (IRS). Pathol Res Pract. 1993, 189: 862-866.CrossRefPubMed Remmele W, Schicketanz K-H: Immunohistochemical determination of estrogen and progesterone receptor content in human breast cancer. Computer-assisted image analysis (QIC score) vs. subjective grading (IRS). Pathol Res Pract. 1993, 189: 862-866.CrossRefPubMed
31.
go back to reference Keating JT, Cviko A, Reithdorf S, Riethdorf L, Quade BJ, Sun D, Duensing S, Sheets EE, Munger K, Crum CP: Ki-67, cyclin E and p16 (INK 4) are complimentary surrogate biomarkers for human papilloma virus-related cervical neoplasia. Am J Surg Pathol. 2001, 25: 894-891.CrossRef Keating JT, Cviko A, Reithdorf S, Riethdorf L, Quade BJ, Sun D, Duensing S, Sheets EE, Munger K, Crum CP: Ki-67, cyclin E and p16 (INK 4) are complimentary surrogate biomarkers for human papilloma virus-related cervical neoplasia. Am J Surg Pathol. 2001, 25: 894-891.CrossRef
32.
go back to reference Klaes R, Friedrich T, Spitkovsky D, Ridder R, Rudy W, Petry U, Dallenbach-Hellweg G, Schmidt D, von Knebel Doeberitz M: Overexpression of p16 (INK 4A) as a specific marker for dysplastic and neoplastic epithelial cells of the cervix uteri. Int J Cancer. 2001, 92: 276-284. 10.1002/ijc.1174.CrossRefPubMed Klaes R, Friedrich T, Spitkovsky D, Ridder R, Rudy W, Petry U, Dallenbach-Hellweg G, Schmidt D, von Knebel Doeberitz M: Overexpression of p16 (INK 4A) as a specific marker for dysplastic and neoplastic epithelial cells of the cervix uteri. Int J Cancer. 2001, 92: 276-284. 10.1002/ijc.1174.CrossRefPubMed
33.
go back to reference Klaes R, Benner A, Friedrich T, Ridder R, Herrington S, Jenkins D, Kurman RJ, Schmidt D, Stoler M, von Knebel Doeberitz M: p16 ink 4a immunohistochemistry improves interobserver agreement in the diagnosis of cervical intraepithelial neoplasia. J Pathol. 2001, 195: 2A- Klaes R, Benner A, Friedrich T, Ridder R, Herrington S, Jenkins D, Kurman RJ, Schmidt D, Stoler M, von Knebel Doeberitz M: p16 ink 4a immunohistochemistry improves interobserver agreement in the diagnosis of cervical intraepithelial neoplasia. J Pathol. 2001, 195: 2A-
34.
go back to reference Murphy N, Bermingham N, Ring M: Immunocytochemical analysis of p16 protein in cervical cancer and cervical intraepithelial neoplasia. J Pathol. 2001, 195: 2A- Murphy N, Bermingham N, Ring M: Immunocytochemical analysis of p16 protein in cervical cancer and cervical intraepithelial neoplasia. J Pathol. 2001, 195: 2A-
35.
go back to reference Ruas M, Peters G: The p16 INK 4a/CDKN2A tumor suppressor and its relatives. Biochem Biophys Acta. 1998, 1378: 115-117. Ruas M, Peters G: The p16 INK 4a/CDKN2A tumor suppressor and its relatives. Biochem Biophys Acta. 1998, 1378: 115-117.
36.
go back to reference Cameron RI, Maxwell P, Jenkins D, MCluggage WG: Immunohistochemical staining with MIB1, bcl-2 and p16 assists in the distinction of cervical glandular intraepithelial neoplasia from tubo-endometrial metaplasia, endometriosis and microglandular hyperplasia. Histopathology. 2002, 41: 313-21. 10.1046/j.1365-2559.2002.01465.x.CrossRefPubMed Cameron RI, Maxwell P, Jenkins D, MCluggage WG: Immunohistochemical staining with MIB1, bcl-2 and p16 assists in the distinction of cervical glandular intraepithelial neoplasia from tubo-endometrial metaplasia, endometriosis and microglandular hyperplasia. Histopathology. 2002, 41: 313-21. 10.1046/j.1365-2559.2002.01465.x.CrossRefPubMed
37.
go back to reference Semczuk A, Stenzel A, Baranowski W, Rozynska K, Cybulski M, Kostuch M, Jakowicki J, Wojcierowski J: Detection of human papillomavirus types 16 and 18 in human neoplastic endometrium: lack of correlation with established prognostic factors. Oncol Reports. 2000, 7: 905-910. Semczuk A, Stenzel A, Baranowski W, Rozynska K, Cybulski M, Kostuch M, Jakowicki J, Wojcierowski J: Detection of human papillomavirus types 16 and 18 in human neoplastic endometrium: lack of correlation with established prognostic factors. Oncol Reports. 2000, 7: 905-910.
38.
go back to reference Brewster WR, Monk BJ, Burger RA, Bergen S, Wilczynski SP: Does human papillomavirus have a role in cancers of the uterine corpus?. Gynecol Oncol. 1999, 75: 51-54. 10.1006/gyno.1999.5534.CrossRefPubMed Brewster WR, Monk BJ, Burger RA, Bergen S, Wilczynski SP: Does human papillomavirus have a role in cancers of the uterine corpus?. Gynecol Oncol. 1999, 75: 51-54. 10.1006/gyno.1999.5534.CrossRefPubMed
39.
go back to reference O'Leary JJ, Landers RJ, Crowley M, Healy I, O'Donovan M, Healy V, Kealy WF, Hogan J, Doyle CT: Human papillomavirus and mixed epithelial tumorsof the endometrium. Hum Pathol. 1998, 29: 383-389. 10.1016/S0046-8177(98)90120-4.CrossRefPubMed O'Leary JJ, Landers RJ, Crowley M, Healy I, O'Donovan M, Healy V, Kealy WF, Hogan J, Doyle CT: Human papillomavirus and mixed epithelial tumorsof the endometrium. Hum Pathol. 1998, 29: 383-389. 10.1016/S0046-8177(98)90120-4.CrossRefPubMed
Metadata
Title
Inclusion of MUC1 (Ma695) in a panel of immunohistochemical markers is useful for distinguishing between endocervical and endometrial mucinous adenocarcinoma*
Authors
Thaer Khoury
Dongfeng Tan
Jianmin Wang
Marilyn Intengan
Jun Yang
Sadir Alrawi
Peisha Yan
James C Byrd
Publication date
01-12-2006
Publisher
BioMed Central
Published in
BMC Clinical Pathology / Issue 1/2006
Electronic ISSN: 1472-6890
DOI
https://doi.org/10.1186/1472-6890-6-1

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