Esophageal Neuroendocrine Carcinoma Research Articles

Long-term survival after conversion surgery for an esophageal neuroendocrine carcinoma: a case report

BackgroundEsophageal neuroendocrine carcinomas (NECs) are extremely rare. Published information on their clinical features, pathological findings, and prognosis is lacking. The optimal treatment for esophageal NECs has not yet been determined because they appear extremely malignant histologically and have a poor prognosis. We here report on a patient with an esophageal NEC who was successfully treated with multidisciplinary therapies.Case presentationThe patient, a 47-year-old man, was admitted to our hospital with dysphagia and weight loss and an ECOG performance status of 3–4. Upper endoscopy showed a large circumferential neoplasm at the esophagogastric junction. Computed tomography showed lymph node metastases around the left gastric artery. Echocardiography raised a suspicion of invasion of the left atrium. Histopathological examination of biopsy tissue revealed diffuse proliferation of small atypical cells resembling naked nuclei with extensive necrosis and degeneration. The cells showed positive staining for CD56, chromogranin A, and synaptophysin on immunohistochemical analysis. Ki67 was positive in over 90% of cells. He was diagnosed with an esophageal NEC that had infiltrated the left atrium; his cancer was therefore inoperable. Because of his poor overall condition, palliative radiotherapy (30 Gy in 15 fractions) was administered, accompanied by nutritional management. This was followed by four courses of chemotherapy with carboplatin plus etoposide, after which the primary tumor and locoregional lymph node metastases were found to have shrunk. Thoracoscopic- and laparoscopic-assisted McKeown esophagectomy were performed. The postoperative pathological diagnosis was NEC pT3pN0M0 Stage II. The patient had a good postoperative course and received two courses of postoperative adjuvant chemotherapy (carboplatin plus etoposide). Currently, 3 years after commencing treatment, there is no evidence of recurrence.ConclusionsAs mentioned above, there is no established treatment regime for esophageal NEC, and the benefits of conversion surgery are unknown. Our patient achieved long-term recurrence-free survival after radiation therapy, chemotherapy, and surgery for an esophageal NEC with left atrial invasion and multiple lymph node metastases. Conversion surgery for esophageal NECs that respond to chemotherapy may contribute to long-term survival.

Advanced esophageal neuroendocrine carcinoma.

Case report of an advanced esophageal neuroendocrine carcinoma with hepatic metastasis.

Comparison of clinicopathological features and survival analysis between esophageal neuroendocrine carcinoma and esophageal squamous cell carcinoma based on the SEER database, alongside nomogram analysis for esophageal neuroendocrine carcinoma.

Esophageal neuroendocrine carcinoma (ENEC) is a rare subtype of esophageal cancer (EC). It presents distinctive clinical and pathological features in comparison to esophageal squamous cell carcinoma (ESCC). To better elucidate the disparities between the two and establish a prognostic prediction model for ENEC, we conducted this study. Data of ENEC and ESCC patients (1975 to 2016) were extracted from the Surveillance, Epidemiology and End Results (SEER) database. Patients with a confirmed pathological diagnosis of ENEC and ESCC were enrolled in the study. The Chi-square test was employed to compare categorical variables, and the median survival time was analyzed using the Kaplan-Meier curve. Training and validation groups were randomly assigned at a ratio of 7:3. Factors with a significance level of <0.05 in the multifactor regression model as well as age were integrated into the nomogram model. Concordance index (C-index), calibration curves, and decision curve analyses (DCA) were generated for model validation. This study encompassed a total of 737 ENEC patients and 29,420 ESCC. Compared to ESCC, ENEC patients had higher probability of liver metastasis (13.8% vs. 1.9%, P<0.001), poor differentiation (68.0% vs. 37.1%, P<0.001), and late SEER stage (52.8% vs. 26.9%, P<0.001). Patients who received either surgery, radiotherapy (RT), or chemotherapy had a significantly longer disease-specific survival (DSS) and overall survival (OS) (all P<0.001). After propensity score matching (PSM), ENEC patients were associated with shorter DSS (7.0 months vs. not reached, P<0.0001) and OS (7.0 vs. 12.0 months, P<0.0001) compared to ESCC. Race, SEER stage, surgery, RT, and chemotherapy were identified as predictors of DSS and were incorporated into the nomogram model together with age. The validation of the model using C-index (0.751 and 0.706, respectively) and calibration curves reflected the better discrimination power of the model. In addition, DCA supported the favorable potential clinical effect of the predictive model. Lastly, a risk classification based on the nomogram also verified the reliability of the model. ENEC and ESCC exhibit distinct clinicopathological features. Patients with ENEC experience significantly poorer survival outcomes compared to those with ESCC. Surgical intervention, radiation therapy, and chemotherapy significantly improve OS and DSS for ENEC patients. The nomogram prediction model, constructed based on age, race, stage, and treatment regimen, demonstrates accurate and effective predictive capabilities for prognostic factors in ENEC patients.

Histology Shift in Esophageal Cancer Between Biopsies and Resections After Neoadjuvant Therapy: A Pilot Study.

Preoperative neoadjuvant therapy followed by resection is the mainstay treatment for locally advanced esophageal adenocarcinoma. We recently observed the histology shift from predominant esophageal adenocarcinoma in the biopsy to neuroendocrine neoplasm with or without adenocarcinoma in the post-treatment resection. The underlying mechanism of this finding is uncertain, and there is limited information in the literature. A total of 11 patients were identified: 10 patients received presurgical chemoradiation and 1 with chemotherapy. All biopsies were diagnosed with adenocarcinoma. When neuroendocrine immunomarkers were retrospectively performed on 5 biopsies, 2 showed focal positivity, although the classic neuroendocrine morphology was not readily appreciated. All resections contained neuroendocrine neoplasm, including 8 of well-differentiated type and 3 of neuroendocrine carcinomas. Two post-treatment esophagectomies consisted of neuroendocrine neoplasm only without residual adenocarcinoma. Upon follow-up, 8 patients died of the disease (median survival = 26 months), and 3 patients were alive after a median follow-up of 14 months. The overall median survival time was better than the reported esophageal neuroendocrine carcinoma (15 months). The 5-year observed survival rate was 11.3%, which was lower than the Surveillance, Epidemiology, and End Results 5-year survival rate of adenocarcinoma (21.8%). We reported a small series of esophageal adenocarcinoma that showed histology shift between biopsy and esophagectomy after neoadjuvant therapy. Our limited data suggest that prognosis of this group is different than the conventional adenocarcinoma. Awareness of this morphological change reminds pathologists to examine the biopsy specimens thoroughly, because recognition of neuroendocrine neoplasm, especially high-grade neuroendocrine component, might potentially affect pre- and post-surgical regimens.

Radiomics model based on contrast-enhanced CT texture features for pretreatment prediction of overall survival in esophageal neuroendocrine carcinoma.

Limited studies have observed the prognostic value of CT images for esophageal neuroendocrine carcinoma (NEC) due to rare incidence and low treatment experience in clinical. In this study, the pretreatment enhanced CT texture features and clinical characteristics were investigated to predict the overall survival of esophageal NEC. This retrospective study included 89 patients with esophageal NEC. The training and testing cohorts comprised 61 (70%) and 28 (30%) patients, respectively. A total of 402 radiomics features were extracted from the tumor region that segmented pretreatment venous phase CT images. The least absolute shrinkage and selection operator (LASSO) Cox regression was applied to feature dimension reduction, feature selection, and radiomics signature construction. A radiomics nomogram was constructed based on the radiomics signature and clinical risk factors using a multivariable Cox proportional regression. The performance of the nomogram for the pretreatment prediction of overall survival (OS) was evaluated for discrimination and calibration. Only the enhancement degree was an independent factor in clinical variable influenced OS. The radiomics signatures demonstrated good predictability for prognostic status discrimination. The radiomics nomogram integrating texture signatures was slightly superior to the nomogram derived from the combined model with a C-index of 0.844 (95%CI: 0.783-0.905) and 0.847 (95% CI: 0.782-0.912) in the training set, and 0.805 (95%CI: 0.707-0.903) and 0.745 (95% CI: 0.639-0.851) in the testing set, respectively. The radiomics nomogram based on pretreatment CT radiomics signature had better prognostic power and predictability of the overall survival in patients with esophageal NEC than the model using combined variables.

Clinicopathological features, treatment modalities, and prognosis of esophageal neuroendocrine carcinoma: A single-center retrospective study.

Esophageal neuroendocrine carcinoma (ENEC) is a rare cancer that is highly malignant and related to a poor prognosis. In this retrospective study we aimed to elucidate the clinical characteristics, diagnosis and management of patients with ENEC and to evaluate the potential prognostic factors. Altogether 82 patients diagnosed with ENEC between January 2009 and December 2020 at the Fudan University Shanghai Cancer Center were retrospectively enrolled. Patients' survival was analyzed using the Kaplan-Meier and log-rank methods. Univariate and multivariate analyses and a Cox regression model were used to identify the prognostic factors. The median overall survival (mOS) was 13 months in all patients. Multivariate analysis revealed that advanced tumor stage (hazard ratio [HR] 2.67, 95% confidence interval [CI] 1.07-6.66, P = 0.0353), liver (HR 3.36, 95% CI 1.53-7.41, P = 0.0026) and lung metastasis (HR 3.37, 95% CI 1.20-9.51, P = 0.0214) were associated with a poor prognosis. While positive chromogranin A (CgA) expression was related to a favorable outcome (HR 0.21, 95% CI 0.09-0.49, P < 0.001). Also, patients had adjustment of chemotherapy (dose reduction or less than three cycles) were prone to a worse prognosis compared with those did not (HR 4.36, 95% CI 2.10-9.08, P < 0.001). In patients with ENEC, advanced cancer stage, adjustment of chemotherapy, liver and lung metastasis were associated with a poor survival, while CgA expression was related to a favorable prognosis.

Esophageal Neuroendocrine Carcinoma Presenting After Definitive Chemoradiation of Squamous Cell Carcinoma in the Same Location

ABSTRACT Esophageal neuroendocrine carcinoma is very rare and highly aggressive. An 85-year-old man with a history of esophageal squamous cell carcinoma in remission presented 4 years after definitive chemoradiation with new-onset dysphagia. Endoscopy with biopsy revealed high-grade malignancy consistent with neuroendocrine carcinoma. Treatment options were limited to chemotherapy because of his metastatic disease, and he unfortunately died 14 months after diagnosis. The occurrence of esophageal neuroendocrine carcinoma in a site of prior squamous cell carcinoma is very uncommon, and this likely represents a case of radiation-induced malignancy. Therefore, when undergoing radiotherapy, patients and providers should discuss the possibility of this life-threatening complication.

MicroRNAs associated with postoperative outcomes in patients with limited stage neuroendocrine carcinoma of the esophagus.

Esophageal neuroendocrine carcinoma (E-NEC) is an aggressive disease with a poor prognosis. The present study aimed to assess the role of surgery in the treatment of patients with resectable E-NEC, and identify a microRNA (miRNA/miR) signature in association with positive postoperative outcomes. Between February 2017 and August 2019, 36 patients with E-NEC who underwent curative surgery at the Japan Neuroendocrine Tumor Society partner hospitals were enrolled in the study. A total of 16 (44.4%) patients achieved disease-free survival (non-relapse group), whereas 20 (55.6%) patients developed tumor relapse (relapse group) during the median follow-up time of 36.5 months (range, 1-242) after surgery with a 5-year overall survival rate of 100 and 10.8%, respectively (P<0.01). No clinicopathological parameters, such as histological type or TNM staging, were associated with tumor relapse. Microarray analysis of 2,630 miRNAs in 11 patients with sufficient quality RNA revealed 12 miRNAs (miR-1260a, -1260b, -1246, -4284, -612, -1249-3p, -296-5p, -575, -6805-3p, -12136, -6822-5p and -4454) that were differentially expressed between the relapse (n=6) and non-relapse (n=5) groups. Furthermore, the top three miRNAs (miR-1246, -1260a and -1260b) were associated with overall survival (P<0.01). These results demonstrated that surgery-based multidisciplinary treatment is effective in a distinct subpopulation of limited stage E-NEC. A specific miRNA gene set is suggested to be associated with treatment outcome.

High-grade large cell neuroendocrine carcinoma of the esophagus: a case report and review of the literature

BackgroundNeuroendocrine carcinomas are extremely rare in the esophagus as they represent less than 0.04% of all neuroendocrine tumors. To date, only 14 cases of poorly differentiated, high-grade esophageal NEC have been described in the literature. The majority of these patients presented with typical dysphagia symptoms. Due to its rarity, no standardized guidelines have been proposed to treat esophageal neuroendocrine carcinoma, although general recommendations suggest surgery with adjuvant chemoradiotherapy as the treatment of choice.Case presentationA 67-year-old previously healthy White male presented with a year-long intermittent nonspecific retrosternal discomfort, with the absence of any other symptoms. Esophagogastroduodenoscopy revealed an ulcerative mass in his lower esophagus, with concern of malignancy. Endoscopic ultrasound-guided biopsy revealed poorly differentiated neuroendocrine carcinoma of the esophagus with metastasis to a diaphragmatic lymph node. He was treated with neoadjuvant chemoradiation followed by surgery, and he has been in remission for over 5 years.ConclusionHere, we review the literature and report a unique case of a patient with a vague presentation of esophageal neuroendocrine carcinoma as he enters his sixth year of survival following neoadjuvant chemoradiotherapy.

Prognostic value of pretreatment 18F-FDG PET/CT metabolic parameters in esophageal high-grade neuroendocrine carcinoma: A bicenter retrospective study.

The aim of this bicentric retrospective study was to assess the prognostic value of 18F-FDG PET/CT in patients with esophageal high-grade neuroendocrine carcinoma (NECs). From the database of two centers, 28 patients affected by esophageal high-grade NECs who underwent 18F-FDG PET/CT before treatment were retrospectively reviewed. Metabolic parameters (SUVmax, SUVmean, tumor-to-blood-pool SUV ratio (TBR), tumor-to-liver SUV ratio (TLR), metabolic tumor volume (MTV), total lesion glycolysis (TLG)) of the primary tumor were measured. Univariate and multivariate analyses were performed for progression-free survival (PFS) and overall survival (OS). After a median follow-up period of 22 months, disease progression occurred in 11 (39.3%) patients, and death occurred in 8 (28.6%) patients. The median PFS was 34 months, and the median OS was not reached. Univariate analyses revealed that among metabolic parameters, only MTV and TLG were significant prognostic factors, while among clinical variables, only distant metastasis was a significant factor for both PFS and OS (P< 0.05). On multivariate analyses, MTV and TLG were independent prognostic factors for both PFS and OS (P< 0.05). In patients with esophageal high-grade NEC, MTV and TLG measured on pretreatment 18F-FDG PET/CT are independently prognostic factors for predicting PFS and OS, and might be used as quantitative prognostic imaging biomarkers.

The different prognostic factors between metastatic and nonmetastatic disease of esophageal neuroendocrine carcinoma.

The specific risk factors of metastatic and nonmetastatic esophageal neuroendocrine carcinoma (NEC) are still uncertain. Whether primary site surgery is necessary for all patients with esophageal NEC is unknown. Patients with esophageal NEC in the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2014 were selected. STATA 12 was used to analyze the clinical and pathological features of esophageal NEC. In total, 241 patients with esophageal NEC were included. Metastatic patients had shorter overall survival than nonmetastatic patients (6.03 versus 11.90 months, respectively). Prognostic factors varied between metastatic and nonmetastatic esophageal NEC. The location of the primary tumor is a key point for the prognosis of esophageal NEC. For nonmetastatic esophageal NEC, patients with tumors in the upper third of the esophagus had the worst survival, and patients with metastatic esophageal NEC with a primary tumor in the lower part of the esophagus tended to have an increased risk of death. Moreover, age ≥68 years (hazard ratio [HR] = 2.05; 95% confidence interval [CI]: 1.28-3.31; P < 0.01) and large cell carcinoma (HR = 2.79; 95% CI: 1.30-6.00; P < 0.01) were independent risk factors in patients with metastatic esophageal NEC. Primary site resection benefited patients with nonmetastatic esophageal NEC (HR = 0.20; 95% CI: 0.07-0.56; P < 0.01) rather than patients with metastatic esophageal NEC (HR = 0.91; 95% CI: 0.29-2.83; P > 0.05). Our study presented that primary tumor location is an important risk factor for nonmetastatic esophageal NEC patients. Age and pathological type are important risk factors for patients with metastatic esophageal NEC. Nonmetastatic esophageal NEC will benefit from primary tumor resection. Systematic treatment is recommended for metastatic esophageal NEC.

S2306 Esophageal Neuroendocrine Carcinoma Presenting After Definitive Chemoradiation of Squamous Cell Carcinoma in the Same Location

S2306 Esophageal Neuroendocrine Carcinoma Presenting After Definitive Chemoradiation of Squamous Cell Carcinoma in the Same Location

Resection of Combined Esophageal Neuroendocrine Carcinoma Treated with Preoperative Chemotherapy: A Case Report

Resection of Combined Esophageal Neuroendocrine Carcinoma Treated with Preoperative Chemotherapy: A Case Report

Clinical characteristics, prognostic factors, and survival trends in esophageal neuroendocrine carcinomas: Apopulation-based study.

Esophageal neuroendocrine carcinoma (ENEC) is an extremely rare type of malignancy. Clinical data of ENEC are limited to case reports and case series. More information is needed on its clinical feature, management, and prognosis. This study collected information of ENEC patients diagnosed pathologically from 2010 to 2018. Data including demographic information, clinical features, and survival trends were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Statistical analyses were performed with STATA/SE 15.1, SPSS 25.0, and GraphPad Prism 8. A total of 283 ENEC patients were included in this study. The small-cell and large-cell subtypes of ENEC possess similar clinical features. The lower third of the esophagus (58%) was the most common location of ENEC. At the time of diagnosis, most ENEC patients were AJCC 7th stage IV (48.1%). Metastasis occurred in more than half of the ENEC patients (53.4%), and the most common metastatic site was the liver (37.1%). Compared with poorly differentiated esophageal squamous cell carcinoma (ESCC), another aggressive malignancy of the esophagus sometimes confused with ENEC because of similar histological features, our study showed differences in tumor location and metastatic rate, but similar poor survival rates. Multivariate survival analysis showed that ENEC located at the middle third of esophagus (p= 0.013), "Brain metastasis" (p= 0.019), and "Liver metastasis" (p< 0.001) were independent predictors of worse outcomes. "Surgery" (p= 0.003), and "Chemotherapy" (p< 0.001) were associated with better survival. A significant proportion of patients with newly diagnosed ENEC presented with metastatic disease. Predictors of poor survival included tumor location, brain metastasis, and liver metastasis. ENEC and poorly differentiated ESCC share certain histological features, but differ in tumor location and metastatic rate. Yet, no standard treatment strategy has been established, but surgery and chemotherapy were related to better outcomes.

Survival According to Primary Tumor Location, Stage, and Treatment Patterns in Locoregional Gastroenteropancreatic High-grade Neuroendocrine Carcinomas.

BackgroundAlthough the gastrointestinal tract (including the pancreas, gastroenteropancreatic (GEP) is the most common site for extrapulmonary neuroendocrine carcinoma (NEC), the current treatment patterns of locoregional GEP NEC and in particular, the role of surgical resection is unclear.MethodsData from the National Cancer Database between 2004 and 2016 were used for this study.ResultsOf 2314 GEP NEC cases (stages I–III), 52.5% were stage III. Colon was the most common site (30%); 30.9% of all cases were small cell morphology. Age, morphology, stage, and primary site were associated with significant differences in treatment patterns. Management of NEC mimicked that of adenocarcinomas arising at the respective sites: colon NEC most likely to be treated with surgery and chemotherapy; anal and esophageal NEC was primarily likely to receive chemotherapy and radiation, and rectal NEC mostly likely to receive trimodality therapy. However, 25%-40% of patients did not undergo surgical resection even at sites typically managed with curative resection, and there was a trend toward lesser resection over time. The prognostic impact of surgical resection was significant across all stages and correlated with variations in survival across primary sites. Even in patients undergoing chemoradiation, surgery was the only prognostic variable that significantly affected survival in stages I–II patients (HR 0.63) and showed a strong trend in stage III (HR 0.77) patients.ConclusionsTreatment patterns in GEP NEC vary considerably according to stage and primary tumor site. Surgery significantly improved survival in stages I–II patients and showed a strong trend in stage III patients regardless of primary tumor location and other perioperative therapies.

Clinicopathological analysis of 67 cases of esophageal neuroendocrine carcinoma and the effect of postoperative adjuvant therapy on prognosis.

The clinicopathological properties of esophageal neuroendocrine carcinoma (ENEC) and its optimal therapy have not been widely studied, as the disease is not common. Consequently, we conducted a retrospective study to analyze the clinical features as well as the prognosis of patients with surgically resected ENEC.The clinicopathological data of patients with ENEC who underwent esophagostomy with regional lymphadenectomy at Jiangsu Province People's Hospital and Jiangsu Provincial Tumor Hospital starting January 2008 until December 2014 were collected.Ninety-two cases of ENEC were part of this study. However, only 67 patients were analyzed and followed up. A univariate model for the Cox proportional hazards revealed that prognosis was associated with postoperative adjuvant therapy, age, and lymph node metastasis (P < .05); a multivariate Cox proportional hazards model showed that postoperative adjuvant therapy was a significant independent prognostic factor. Postoperative adjuvant therapy directly affected overall survival, with a significant disparity noted between the groups (P = .022). In this study, patients who received adjuvant therapy had an average time of survival of 39 months (interquartile range: 27.068–50.932 months), while those who did not receive adjuvant therapy had an average survival time of 13 months (interquartile range: 10.129–15.871 months). The survival time was longer in the treated group than in the untreated group (hazard ratio = 0.47; 95% confidence interval: 0.23–0.94; P = .034).ENEC is a heterogeneous tumor with a very poor prognosis. Combining surgery with adjuvant and/or chemotherapy significantly prolongs the survival of patients, and the optimal treatment for ENEC should be determined with future prospective studies.

Nivolumab in combination with radiotherapy for metastatic esophageal neuroendocrine carcinoma after esophagectomy: a case report

BackgroundMetastatic neuroendocrine carcinoma has an extremely poor prognosis, and no effective second-line treatment is available. Herein, we describe a case of multiple metastases after primary resection of esophageal neuroendocrine carcinoma successfully treated with nivolumab plus radiotherapy in a short time.Case presentationA man in his 70s presented to our hospital after an abnormality was detected on an upper gastrointestinal series. Upper gastrointestinal endoscopy revealed a type 2 tumor spanning the endothelial cell junction to the abdominal esophagus. Histopathological examination of the biopsy confirmed a diagnosis of esophageal neuroendocrine carcinoma. The patient had no distant metastases. Thoracoscopic esophagectomy with three-field lymph node dissection was performed. Histopathological examination confirmed a diagnosis of esophageal neuroendocrine carcinoma with features of adenoid cystic-like carcinoma and squamoid pattern (pT2 [MP], INF a, ly1, v1 [EVG], pIM0, pDM0, pRM0, pN1 [1/28], M0; Stage II), which was positive for synaptophysin. The postoperative course was good, with no complications. The patient was treated with 100 mg of irinotecan and 100 mg of cisplatin, administered every 4 weeks, as postoperative adjuvant chemotherapy. Grade 3 loss of appetite was observed, and adjuvant chemotherapy was discontinued after four cycles of first-line treatment. A positron emission tomography–computed tomography scan 3 years after surgery showed abnormal uptake in the subaortic, left hilar, and left axillary lymph nodes, and in a mass in the right lung apex. The patient was diagnosed with metastatic esophageal neuroendocrine carcinoma postoperatively. First-line treatment could not be repeated due to toxicity from the initial treatment. Nivolumab (240 mg every 2 weeks) was administered as second-line treatment, and radiotherapy was started (56 Gy delivered in 28 fractions to the local [subaortic and hilar] lymph nodes). After 10 cycles of nivolumab in combination with radiotherapy (56 Gy), a positron emission tomography–computed tomography scan showed disappearance of all lesions. A complete response was achieved. Maintenance therapy (240 mg of nivolumab) was continued. No recurrence has been observed for 42 months.ConclusionsWe experienced a case in which nivolumab in combination with radiotherapy was effective for metastatic esophageal neuroendocrine carcinoma after primary resection.

812 PROGRAMMED CELL DEATH PROTEIN 1/PROGRAMMED DEATH LIGAND 1 AND HLA-CLASS I ARE POTENTIAL THERAPEUTIC TARGETS IN ESOPHAGEAL NEUROENDOCRINE CARCINOMA

Abstract Esophageal neuroendocrine carcinoma (NEC) is a rare and aggressive subtype with a poor prognosis. Pembrolizumab was recommended for the treatment of PD-L1 positive tumors in esophageal cancer and the combined positive score (CPS) was reported to be a better predictor of efficacy compared to the tumor proportion score (TPS). We investigated the expression profile of potential therapeutic targets (PD-L1, HLA class I, Mismatch repair (MMR) proteins) and tumor infiltrating lymphocytes (TILs) in esophageal NEC. Methods 15 NECs of the esophagus including mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) with squamous cell carcinoma (SCC) component were investigated in the study. The expression of PD-L1 (quantitatively evaluated by CPS and TPS), HLA class I, and MMR protein expression were examined immunohistochemically. TIL abundance was examined semiquantitatively by observation of H&amp;E slides. Results Nine (60%) showed a CPS ≥ 1, five (33%) showed a CPS ≥10, and five cases showed a TPS ≥1. Survival analysis showed a significantly longer overall survival in the CPS ≥1 group than in the CPS &amp;lt;1 group. Deficiency of MMR protein was not observed in any cases. HLA-Class I expression was retained in 10 (67%), and loss of HLA-Class I was significantly correlated with frequent lymph node metastasis, high TNM Stage, and low TIL. Three showed both PD-L1 CPS ≥ 10 and high TIL. Conclusion In esophageal NEC, PD-L1 positivity and preserved HLA-Class I expression were frequently observed, and PD-L1 CPS ≥ 1 was significantly associated with the better prognosis of esophageal NEC. Therefore, the PD-1/PD-L1 pathway and HLA-class I are thought to be potential therapeutic targets in esophageal neuroendocrine carcinoma.

ASO Visual Abstract: Diagnostic Immunostaining and Tumor Markers Predict Prognosis of Patients with Esophageal Neuroendocrine Carcinoma

ASO Visual Abstract: Diagnostic Immunostaining and Tumor Markers Predict Prognosis of Patients with Esophageal Neuroendocrine Carcinoma

Diagnostic Immunostaining and Tumor Markers Predict the Prognosis of Esophageal Neuroendocrine Cell Carcinoma Patients.

Esophageal neuroendocrine carcinoma (ENEC) has a poor prognosis, and predicting the prognosis by examining various markers may contribute to the determination of treatment strategies. Therefore, a multiple-institution retrospective study was performed to identify biomarkers using diagnostic immunohistochemistry and serum tumor markers that predict the prognosis of patients with ENEC. The results of immunohistochemical examination and serum tumor markers were extracted from the data of 141 ENEC patients at 39 institutions certified by the Japan Esophageal Society. The study then examined correlations between these data and prognosis or treatment effects. The ENEC patients with positively for all expression of synaptophysin (Syn), chromogranin A (CgA), and CD56 had a significantly worse prognosis than the patients with other expression patterns. Additionally, surgery and chemoradiotherapy were significantly more effective treatments than chemotherapy for the patients who were not positive for all expressions of Syn, CgA, and CD56. In terms of serum tumor markers, the patients with a high neuron-specific enolase (NSE) value had a significantly worse prognosis than the patients with a normal NSE value, and complete response (CR) cases treated with chemotherapy were significantly fewer in the high-NSE group. The results of multivariate analysis demonstrated that high NSE levels were an independent poor prognostic factor for esophageal endocrine cell carcinoma. This study showed that positivity for all expressions of Syn, CgA, and CD56, and a high NSE value were significantly worse prognostic factors for ENEC patients than other expression patterns and may be important prognostic biomarkers of ENEC.