High-incidence of PTEN mutations in Chinese patients with primary small cell carcinoma of the esophagus

Abstract

Background: Primary small cell carcinoma of the esophagus (PSCCE) is a rare and aggressive tumor with poor prognosis. The aim of this study was to investigate the existence of EGFR, KRAS, PIK3CA and PTEN mutations in PSCCE.

Methods: Clinical-pathological data and paraffin-embedded specimens were collected from 38 patients. Exons 18 to 21 of EGFR, KRAS and PIK3CA status were analyzed by real-time PCR based on ARMS and Scorpion technology in all patients, and the PTEN gene was also screened using real-time PCR and high-resolution melting curve analysis (HRMA).

Results: Only 1 (2.63%) out of 38 patients had EGFR mutations in L858R missense, and KRAS and PIK3CA were not found in the mutational spot in all patients. However, PTEN mutations presented in 14 (36.84%) out of 38 patients, including exon 5 coding for PTEN missense mutation (n =4, 10.53%), exon 6 (n =7, 18.42%), concurrent exon 5 and exon 6 (n =2, 5.26%), and exon 8 (n =1, 2.63%). Concurrent mutations of these genes were not detected in all samples. No statistically significant associations were found between the clinicopathological features and the mutation status of PTEN.

Conclusions: The incidence of PTEN mutations in Chinese patients with PSCCE was higher than that of previous reports in other histological subtypes of esophageal cancer.

Figure 1

A representative case of primary small cell carcinoma of the esophagus. Biopsy materials were shown in the histopathologic examination, and tumoral cells in the sample indicated CK, CgA, CD56, Syn, TTF-1 and Ki-67 with a positive immunoreactivity by immunohistochemical examination. (Magnification, ×200).

Figure 2

Amplification plots for PTEN mutations in exon 5,6,8 using High-resolution melting analysis. (A,B,C). Amplification plots for a sample containing no mutated in PTEN gene. A, exon 5; B, exon 6; C, exon 8. (D,E,F). Amplification plots for a sample containing mutated exon 5 and exon 6 in PTEN gene. D, exon 5; E, exon 6; F, exon 8. (G,H,I). Amplification plots for a sample containing a mutated exon 8 in PTEN gene. G, exon 5; H, exon 6; I, exon 8. The Y-axis shows the relative fluorescence for a measurement of the change in fluorescent signal versus a passive reference signal, X-axis shows the temperature (°C). Each sample was analyzed in triplicate or duplicate.