Immunohistochemical expression profiles of mucin antigens in salivary gland mucoepidermoid carcinoma: MUC4- and MUC6-negative expression predicts a shortened survival in the early postoperative phase

Kie Honjo, Tsubasa Hiraki, Michiyo Higashi, Hirotsugu Noguchi, Mitsuharu Nomoto, Takuya Yoshimura, Surinder Kumar Batra, Suguru Yonezawa, Ichiro Semba, Norifumi Nakamura, Akihide Tanimoto, Sohsuke Yamada

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

In mucoepidermoid carcinoma (MEC), the most common salivary gland carcinoma, there is a lack of novel prognostic markers, but post-operative early recurrence strongly affects the clinical course and a poor outcome. It is critical to predict which MEC patients are prone to develop recurrence/metastases. Mucins play pivotal roles in influencing cancer biology, thus affecting cell differentiation, adhesion, carcinoma invasion, aggressiveness and/or metastatic potential. Our aim is to elucidate the significance of expression profiles for mucins, particularly MUC4 and MUC6, and their correlations with various clinicopathological features and recurrence in salivary gland MECs. We performed immunohistochemical analyses on patients with surgically resected primary MEC using antibodies against mucin core proteins MUC4/8G7 and MUC6/CLH5 in 73 paraffin-embedded samples. Recurrence was noted in 15 of 73 (20.5%) patients. MUC4 or MUC6 expression was considered to be negative when <30% or 0% of the MEC cells showed positive staining, respectively. MUC4- and/or MUC6- negative expression respectively and variably showed a significant relationship to pathological tumor high-grade, the presence of lymphovascular invasion, lymph node metastasis and/or tumor-related death. In addition, MUC4 showed significantly negative co-expression with MUC6. Kaplan-Meier analyses revealed that not only single MUC4/6-negative expression but also the combination of both predicted significantly shorter disease-free and disease-specific survivals in MECs, especially within the first two years postoperatively. Therefore, each mucin plays a pivotal role in the pathogenesis of MEC progression. The detection of MUC4 and/or MUC6 might be a powerful parameter in the clinical management of MECs in the early postsurgical phase.

Original languageEnglish (US)
Pages (from-to)201-213
Number of pages13
JournalHistology and Histopathology
Volume33
Issue number2
DOIs
StatePublished - Feb 2018

Fingerprint

Mucoepidermoid Carcinoma
Mucins
Salivary Glands
Antigens
Survival
Recurrence
Neoplasm Metastasis
Carcinoma
Neoplasms
Kaplan-Meier Estimate
Cell Adhesion
Paraffin
Disease-Free Survival
Cell Differentiation
Lymph Nodes
Staining and Labeling
Antibodies
Proteins

Keywords

  • Disease-free survival (DFS)
  • Disease-specific survival (DSS)
  • Immunohistochemistry
  • MUC4
  • MUC6
  • Mucoepidermoid carcinoma (MEC)

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology

Cite this

Immunohistochemical expression profiles of mucin antigens in salivary gland mucoepidermoid carcinoma : MUC4- and MUC6-negative expression predicts a shortened survival in the early postoperative phase. / Honjo, Kie; Hiraki, Tsubasa; Higashi, Michiyo; Noguchi, Hirotsugu; Nomoto, Mitsuharu; Yoshimura, Takuya; Batra, Surinder Kumar; Yonezawa, Suguru; Semba, Ichiro; Nakamura, Norifumi; Tanimoto, Akihide; Yamada, Sohsuke.

In: Histology and Histopathology, Vol. 33, No. 2, 02.2018, p. 201-213.

Research output: Contribution to journalArticle

Honjo, Kie ; Hiraki, Tsubasa ; Higashi, Michiyo ; Noguchi, Hirotsugu ; Nomoto, Mitsuharu ; Yoshimura, Takuya ; Batra, Surinder Kumar ; Yonezawa, Suguru ; Semba, Ichiro ; Nakamura, Norifumi ; Tanimoto, Akihide ; Yamada, Sohsuke. / Immunohistochemical expression profiles of mucin antigens in salivary gland mucoepidermoid carcinoma : MUC4- and MUC6-negative expression predicts a shortened survival in the early postoperative phase. In: Histology and Histopathology. 2018 ; Vol. 33, No. 2. pp. 201-213.
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abstract = "In mucoepidermoid carcinoma (MEC), the most common salivary gland carcinoma, there is a lack of novel prognostic markers, but post-operative early recurrence strongly affects the clinical course and a poor outcome. It is critical to predict which MEC patients are prone to develop recurrence/metastases. Mucins play pivotal roles in influencing cancer biology, thus affecting cell differentiation, adhesion, carcinoma invasion, aggressiveness and/or metastatic potential. Our aim is to elucidate the significance of expression profiles for mucins, particularly MUC4 and MUC6, and their correlations with various clinicopathological features and recurrence in salivary gland MECs. We performed immunohistochemical analyses on patients with surgically resected primary MEC using antibodies against mucin core proteins MUC4/8G7 and MUC6/CLH5 in 73 paraffin-embedded samples. Recurrence was noted in 15 of 73 (20.5{\%}) patients. MUC4 or MUC6 expression was considered to be negative when <30{\%} or 0{\%} of the MEC cells showed positive staining, respectively. MUC4- and/or MUC6- negative expression respectively and variably showed a significant relationship to pathological tumor high-grade, the presence of lymphovascular invasion, lymph node metastasis and/or tumor-related death. In addition, MUC4 showed significantly negative co-expression with MUC6. Kaplan-Meier analyses revealed that not only single MUC4/6-negative expression but also the combination of both predicted significantly shorter disease-free and disease-specific survivals in MECs, especially within the first two years postoperatively. Therefore, each mucin plays a pivotal role in the pathogenesis of MEC progression. The detection of MUC4 and/or MUC6 might be a powerful parameter in the clinical management of MECs in the early postsurgical phase.",
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AU - Hiraki, Tsubasa

AU - Higashi, Michiyo

AU - Noguchi, Hirotsugu

AU - Nomoto, Mitsuharu

AU - Yoshimura, Takuya

AU - Batra, Surinder Kumar

AU - Yonezawa, Suguru

AU - Semba, Ichiro

AU - Nakamura, Norifumi

AU - Tanimoto, Akihide

AU - Yamada, Sohsuke

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AB - In mucoepidermoid carcinoma (MEC), the most common salivary gland carcinoma, there is a lack of novel prognostic markers, but post-operative early recurrence strongly affects the clinical course and a poor outcome. It is critical to predict which MEC patients are prone to develop recurrence/metastases. Mucins play pivotal roles in influencing cancer biology, thus affecting cell differentiation, adhesion, carcinoma invasion, aggressiveness and/or metastatic potential. Our aim is to elucidate the significance of expression profiles for mucins, particularly MUC4 and MUC6, and their correlations with various clinicopathological features and recurrence in salivary gland MECs. We performed immunohistochemical analyses on patients with surgically resected primary MEC using antibodies against mucin core proteins MUC4/8G7 and MUC6/CLH5 in 73 paraffin-embedded samples. Recurrence was noted in 15 of 73 (20.5%) patients. MUC4 or MUC6 expression was considered to be negative when <30% or 0% of the MEC cells showed positive staining, respectively. MUC4- and/or MUC6- negative expression respectively and variably showed a significant relationship to pathological tumor high-grade, the presence of lymphovascular invasion, lymph node metastasis and/or tumor-related death. In addition, MUC4 showed significantly negative co-expression with MUC6. Kaplan-Meier analyses revealed that not only single MUC4/6-negative expression but also the combination of both predicted significantly shorter disease-free and disease-specific survivals in MECs, especially within the first two years postoperatively. Therefore, each mucin plays a pivotal role in the pathogenesis of MEC progression. The detection of MUC4 and/or MUC6 might be a powerful parameter in the clinical management of MECs in the early postsurgical phase.

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