Aberrant expression of MUC4 in ovarian carcinoma

Diagnostic significance alone and in combination with MUC1 and MUC16 (CA125)

Subhash Chauhan, Ajay P. Singh, Fernanda Ruiz, Sonny L. Johansson, Maneesh Jain, Lynette M. Smith, Nicolas Moniaux, Surinder K. Batra

Research output: Contribution to journalArticle

94 Citations (Scopus)

Abstract

Mucins are being implicated in diagnosis, prognosis, and as therapeutic targets due to their aberrant expression in a variety of carcinomas. Here, we have analyzed the expression of MUC4 and have compared its potential usefulness in early detection and prognosis of ovarian carcinoma alone and in combination with other mucin antigens, MUC1 and MUC16. Clinical significance of the differential mucin expression was evaluated by grouping the tumor samples in early (stage I and II) and advanced (stage III and IV) stage cases and histological subtypes (serous, mucinous, endometrioid and clear cell). Correlation of these mucins with patient's survival (n=63) was determined by Kaplan-Meier analysis in order to predict their prognostic value. MUC4 showed significant overexpression in tumor cases (P<0.0001) with highest incidence (92.0%) among all three mucins. A significant overexpression of MUC1 (P<0.018) and MUC16 (P<0.0001) was also observed in 83.0 and 79.0% of tumor samples, respectively. Notably, MUC4 expression was significantly higher (P≤0.004) compared to both MUC1 and MUC16 in early-stage ovarian tumor samples with 100% incidence. In advanced stage ovarian tumors, all the mucins displayed overall comparable expression, nonetheless, MUC4 had highest prevalence (88.0%) compared to MUC1 (84.0%) and MUC16 (81.0%). A combined panel of MUC4 with MUC16 detected 100% of the late-stage tumor cases without compromising the specificity. Among histological subtypes, only MUC4 displayed 100% (n=5) sensitivity in mucinous ovarian tumors, while MUC1 and MUC16 detected 40 and 20% cases, respectively. The expression of MUC4, however, did not significantly correlate with the survival of the ovarian cancer patient, while a significant correlation of MUC16 with poor prognosis was observed. In conclusion, our study demonstrates that MUC4 could be a potential candidate marker for early diagnosis of epithelial ovarian carcinoma and can be utilized in combination with MUC16 to achieve greater sensitivity for the detection of late-stage tumors.

Original languageEnglish (US)
Pages (from-to)1386-1394
Number of pages9
JournalModern Pathology
Volume19
Issue number10
DOIs
StatePublished - Oct 21 2006
Externally publishedYes

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Mucins
Carcinoma
Neoplasms
Survival
Incidence
Kaplan-Meier Estimate
Ovarian Neoplasms
Early Diagnosis
Antigens

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

Aberrant expression of MUC4 in ovarian carcinoma : Diagnostic significance alone and in combination with MUC1 and MUC16 (CA125). / Chauhan, Subhash; Singh, Ajay P.; Ruiz, Fernanda; Johansson, Sonny L.; Jain, Maneesh; Smith, Lynette M.; Moniaux, Nicolas; Batra, Surinder K.

In: Modern Pathology, Vol. 19, No. 10, 21.10.2006, p. 1386-1394.

Research output: Contribution to journalArticle

Chauhan, Subhash ; Singh, Ajay P. ; Ruiz, Fernanda ; Johansson, Sonny L. ; Jain, Maneesh ; Smith, Lynette M. ; Moniaux, Nicolas ; Batra, Surinder K. / Aberrant expression of MUC4 in ovarian carcinoma : Diagnostic significance alone and in combination with MUC1 and MUC16 (CA125). In: Modern Pathology. 2006 ; Vol. 19, No. 10. pp. 1386-1394.
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abstract = "Mucins are being implicated in diagnosis, prognosis, and as therapeutic targets due to their aberrant expression in a variety of carcinomas. Here, we have analyzed the expression of MUC4 and have compared its potential usefulness in early detection and prognosis of ovarian carcinoma alone and in combination with other mucin antigens, MUC1 and MUC16. Clinical significance of the differential mucin expression was evaluated by grouping the tumor samples in early (stage I and II) and advanced (stage III and IV) stage cases and histological subtypes (serous, mucinous, endometrioid and clear cell). Correlation of these mucins with patient's survival (n=63) was determined by Kaplan-Meier analysis in order to predict their prognostic value. MUC4 showed significant overexpression in tumor cases (P<0.0001) with highest incidence (92.0{\%}) among all three mucins. A significant overexpression of MUC1 (P<0.018) and MUC16 (P<0.0001) was also observed in 83.0 and 79.0{\%} of tumor samples, respectively. Notably, MUC4 expression was significantly higher (P≤0.004) compared to both MUC1 and MUC16 in early-stage ovarian tumor samples with 100{\%} incidence. In advanced stage ovarian tumors, all the mucins displayed overall comparable expression, nonetheless, MUC4 had highest prevalence (88.0{\%}) compared to MUC1 (84.0{\%}) and MUC16 (81.0{\%}). A combined panel of MUC4 with MUC16 detected 100{\%} of the late-stage tumor cases without compromising the specificity. Among histological subtypes, only MUC4 displayed 100{\%} (n=5) sensitivity in mucinous ovarian tumors, while MUC1 and MUC16 detected 40 and 20{\%} cases, respectively. The expression of MUC4, however, did not significantly correlate with the survival of the ovarian cancer patient, while a significant correlation of MUC16 with poor prognosis was observed. In conclusion, our study demonstrates that MUC4 could be a potential candidate marker for early diagnosis of epithelial ovarian carcinoma and can be utilized in combination with MUC16 to achieve greater sensitivity for the detection of late-stage tumors.",
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AU - Johansson, Sonny L.

AU - Jain, Maneesh

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AU - Moniaux, Nicolas

AU - Batra, Surinder K.

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