J Korean Med Sci.  2011 Oct;26(10):1277-1285. 10.3346/jkms.2011.26.10.1277.

Carcinoma ex Pleomorphic Adenoma of the Salivary Glands: Distinct Clinicopathologic Features and Immunoprofiles Between Subgroups According to Cellular Differentiation

• Kim JW
• Kwon GY
• Roh JL
• Choi SH
• Nam SY
• Kim SY
• Cho KJ

• KMID: 1785983
• DOI: http://doi.org/10.3346/jkms.2011.26.10.1277

Abstract

In carcinoma ex pleomorphic adenoma (CXPA), pleomorphic adenoma (PA) and diverse carcinoma components showing luminal (ductal) or non-luminal (myoepithelial) differentiation coexist. To elucidate the clinicopathological implications of cellular differentiation in CXPA and the potential role of p53, vascular endothelial growth factor (VEGF), c-erbB-2, c-kit, and glucose transporter 1 (Glut-1) in carcinogenesis, we analyzed 11 CXPAs with luminal differentiation (CXPAs-LD) and 6 CXPAs with non-luminal differentiation (CXPAs-NLD) and compared protein expressions in residual PAs and carcinomas by immunohistochemistry. Among the CXPAs-LD, 5 were invasive and 8 were histologically high-grade tumors. The 5-year survival rate was 72.7%. P53, c-erbB-2, VEGF, and Glut-1 were more immunoreactive in carcinoma components than in PAs (P = 0.008, 0.004, 0.002, and 0.024, respectively); c-erbB-2 overexpression was associated with high histological grade (P = 0.024). Carcinoma components frequently lacked c-kit expression (P = 0.009). CXPAs-NLD were all low-grade and invasive with a larger mean tumor size (5.2 cm) than CXPAs-LD (3.3 cm) (P = 0.040). The patients remained disease-free without significant immunohistochemical expression. The immunoprofiles and clinical course of CXPA differed according to cellular differentiation. Therefore, it is important to report the histological subtype and to assess potential biomarkers in diagnostic and therapeutic trials.

Keyword

Carcinoma ex Pleomorphic Adenoma; p53; c-erbB-2; Vascular Endothelial Growth Factor; c-kit; Glucose Transporter 1; Histological Types; Prognosis

MeSH Terms

Adenoma, Pleomorphic/*immunology/metabolism/*pathology
Adult
Aged
Carcinoma/*immunology/metabolism/*pathology
Cell Differentiation
Female
Glucose Transport Proteins, Facilitative/metabolism
Humans
Male
Middle Aged
Proto-Oncogene Proteins c-kit/metabolism
Receptor, erbB-2/metabolism
Salivary Gland Neoplasms/*immunology/metabolism/*pathology
Tumor Markers, Biological/*analysis
Tumor Suppressor Protein p53/metabolism
Vascular Endothelial Growth Factor A/metabolism

Figure

• 

  Fig. 1 In CXPA-LD, strong immunohistochemical staining for p53 (A), c-erbB-2 (B), VEGF (C), and Glut-1 (D) was observed in the malignant components (top right), whereas no immunohistochemical reaction to the biomarkers was observed in the residual PA components (bottom left).

• 

  Fig. 2 C-kit expression in residual PA and malignant components. In PA, strong membranous positivity was noted in the luminal cells of duct-like structures (A, B-top right), but in noninvasive and invasive components of CXPA-LD, the result of c-kit immunohistochemical staining was negative (B-bottom left and C). In CXPA-NLD with EMC subtype, c-kit was expressed only in the inner luminal cells of ductal structures (D).

• 

  Fig. 3 In CXPA-NLD, focally positive staining for Bcl-2 (A) and p53 (B) was observed in the malignant components. Also, positive immunohistochemical staining for c-erbB-2 (score 1+, [C]) and Glut-1 (high expression, [D]) was noted in some carcinoma cells.

• 

  Fig. 4 Comparison of the expression rates of biomarkers between carcinoma ex pleomorphic adenomas with luminal and non-luminal differentiations in malignant components. p53 and c-erbB-2 overexpression rates in CXPA-LD are significantly higher than those in CXPA-NLD. *Statistically significant (P ≤ 0.05)

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