Characterization of tissue chromogranin A (CgA) immunostaining and clinicohistopathological changes for the 125 Chinese patients with primary small cell carcinoma of the esophagus

Abstract

The rarity of primary small cell carcinoma of the esophagus (PSCE) has limited the clinical feature and survival analysis with large sample size. Tissue chromogranin A (CgA) protein expression has been reported to be a useful biomarker for diagnosing PSCE. Interestingly, recent studies have indicated tissue CgA as a significant prognostic marker in multiple human cancers, but without PSCE. The present study, thus, was undertaken to characterize the clinicopathological changes and to evaluate the associations of tissue CgA expression with clinical response on Chinese PSCE patients. All the 125 PSCE patients were enrolled from our 500,000 esophageal and gastric cardia carcinoma databases (1973-2015), constructed by the cooperative team from more than 700 hospitals in China and established by Henan Key Laboratory for Esophageal Cancer Research in Henan, China. Immunostaining for CgA showed that CgA was mainly located in cytoplasm of tumor cells with a positive detection rate of 44.6%. The CgA positive expression rate in PSCE at lower segment of the esophagus (72.2%) was higher than that at middle segment (41.5%) (P = 0.001). However, CgA protein expression did not correlated with lymph node metastasis (P = 0.767), TNM staging (P = 0.740), tumor invasion (P = 0.253), gender (P = 0.262), and age (P = 0.250). Multivariate survival analysis showed that the patients with higher CgA protein expression had a superior long survival than those without CgA expression (P = 0.037). The clinicopathological analysis showed that PSCE occurred predominantly in male (M:F = 1.9:1) at the middle segment (68%) of the esophagus. Histologically, 89.6% were pure PSCE and 10.4% were mixed type with either squamous cell carcinoma (8%) or adenocarcinoma (2.4%). It was noteworthy that, with the in-depth invasion from T1 to T2 and T3, the positive lymph node metastasis rate increased dramatically from 38%, 56% to 74%, respectively. The survival rates of 1-, 2-, 3-, and 5-year were 64%, 35%, 18%, and 7%, respectively. The Kaplan-Meier survival analysis showed that the young patients (≤60 years) had longer survival than the elderly (P = 0.011). Interestingly, multivariate survival analysis revealed that the patients with mixed PSCE had a significantly better survival than those with pure PSCE (P = 0.015). Furthermore, the median survival time for the patients with and without lymph node metastasis was 1.16 and 2.03 years, respectively. But, the difference was not significant (P = 0.143). Univariate analysis did not show any survival influence by gender, tumor location, tumor invasion depth, and TNM staging. It was noteworthy that, of the 13 early PSCE patients (T1N0M0), only one patient had more than 5 year survival, the others died with less than one or two year (65%). The present study indicates that the PSCE is of badly worsen prognosis, even in the pathological early stage. Tissue CgA protein expression is a promising maker not only for diagnosis and also for prognosis. Further assessment is needed to establish specific PSCE pathological sta...

Combined surgical treatment of esophageal cancer and coronary heart diseases in elderly patients

“…Surgical treatment of malignant diseases can be either simultaneously performed with CABG or via a staged approach a few weeks later. However, whether to select either one-stage or two-stage operation remains controversial [ 12 , 13 ]. A two-stage procedure is two surgical traumas, which may delay the tumor resection and doubles postoperative pains and treatment costs.…”

“…The simultaneous procedure has gradually been adopted to perform various cardiac and noncardiac operations, including pulmonary lobectomy, esophagectomy, gastrectomy, and colectomy [ 14 , 15 ]. This approach has been mainly performed in thoracic carcinoma patients and may solve two problems through a single incision [ 12 , 15 ]. However, in China which has a large population, there are few reports of combined esophagectomy and off-pump CABG.…”

“…However, in China which has a large population, there are few reports of combined esophagectomy and off-pump CABG. By extensively reviewing relevant literature [ 12 , 16 ], we present the largest single-center report in China so far. The simultaneous surgeries may prolong the anesthesia time and surgical time and increase the postoperative heparinization-related bleeding risks.…”

Prognostic value of immunohistochemical factors in esophageal small cell carcinoma (ESCC): analysis of clinicopathologic features of 73 patients

“…The results failed to testify the prognostic value of Ki67, but showed that negative TTF-1, NSE, Syn or CgA staining was related with a poor survival. In a study enrolled 125 Chinese patients with ESCC showed patients with higher CgA protein expression had a superior long survival than those without CgA expression (P=0.037) (33). Studies about other types of tumor concluded that the percentage of tumor cells with the ability to produce neuroendocrine markers was a significant independent prognostic factor associated with favorable outcomes (24,34,35).…”

Differential expression of neuroendocrine markers, TTF-1, p53, and Ki-67 in cervical and pulmonary small cell carcinoma

“…[ 1 ] SCC may also be found in digestive tract, cervix, ovary, bladder, prostate, and endometrium. [ 2 – 5 ] Although SCC can be found in different anatomic sites, similarities, such as histological appearance, immunohistochemical expression of epithelial and neuroendocrine markers, common involvement of lymph nodes and vessels invasion, hematogenous metastasis, and unfavorable prognosis, can be observed. [ 3 ] However, the risk factors are usually different.…”