[A Case of Recurrent Breast Cancer That Was BRCA1 Pathogenic Variant-Positive Successfully Treated with PARP Inhibitor].

The patient was a 51-year-old woman at the time of diagnosis of left breast cancer. She underwent a mastectomy and axillary dissection. Pathological findings were invasive ductal carcinoma of the breast, tumor diameter 25 mm, and metastasis in 2 of 16 removed axillary lymph nodes. The subtype was triple negative. Postoperative chemotherapy was administered, and the patient was followed by follow-up imaging. At the age of 63 years, ultrasonography showed local recurrence, and local mass excision was performed. Genetic abnormalities were suspected since she had a family history of breast cancer, and it was a recurrent case. After genetic counseling, she underwent genetic testing, which revealed a BRCA1 pathogenic variant, so we initiated imaging surveillance. At age 65, a chest CT scan was performed due to respiratory symptoms, and she was diagnosed with multiple lung metastases. Respiratory symptoms improved at the examination 1 month after administration of Poly ADP ribose polymerase(PARP)inhibitor, and the metastatic masses shrank at the CT scan 3 months later. She continues to maintain CR and has no respiratory symptoms at present.

HIF-1α stimulates the progression of oesophageal squamous cell carcinoma by activating the Wnt/ß-catenin signalling pathway.

BACKGROUND: This study aimed to clarify the significance of the crosstalk between hypoxia-inducible factor-1α (HIF-1α) and the Wnt/ß-catenin pathway in oesophageal squamous cell carcinoma (ESCC). METHODS: The oncogenic role of HIF-1α in ESCC was investigated using in vitro and in vivo assays. The clinicopathological significance of HIF-1α, ß-catenin and TCF4/TCF7L2 in ESCC were evaluated using quantitative real-time PCR and immunohistochemistry. RESULTS: The expression level of HIF-1α, ß-catenin, and TCF4/TCF7L2 in T.Tn and TE1 cell lines were elevated under hypoxia in vitro. HIF-1α knockdown suppressed proliferation, migration/invasion and epithelial-mesenchymal transition (EMT) progression, induced G0/G1 cell cycle arrest, promoted apoptosis and inhibited 5-fluorouracil chemoresistance in vitro. In vivo assays showed that HIF-1α is essential in maintaining tumour growth, angiogenesis, and 5-fluorouracil chemoresistance. Mechanically, we identified the complex between HIF-1α and ß-catenin, HIF-1α can directly bind to the promoter region of TCF4/TCF7L2. The mRNA level of HIF-1α, ß-catenin and TCF4/TCF7L2 were increased in ESCC tumour tissues compared to the corresponding non-tumour tissues. High levels of HIF-1α and TCF4/TCF7L2 expression were correlated with aggressive phenotypes and poor prognosis in ESCC patients. CONCLUSIONS: HIF-1α serves as an oncogenic transcriptional factor in ESCC, probably by directly targeting TCF4/TCF7L2 and activating the Wnt/ß-catenin pathway.

SIRT1 Expression Is a Promising Prognostic Biomarker in Esophageal Squamous Cell Carcinoma: A Systematic Review and Meta-analysis.

Background/Aim: Several articles have assessed the prognostic significance of the expression of sirtuin 1 (SIRT1) in esophageal squamous cell carcinoma (ESCC). However, evidence in this field is insufficient. Thus, we conducted a meta-analysis to investigate the prognostic and clinical impact of SIRT1 expression in ESCC. Materials and Methods: We searched the PubMed, Cochrane Library, and Web of Science databases for articles on the expression of SIRT1 and clinicopathological features in patients with ESCC. A meta-analysis was conducted. Results: Four studies with 429 patients were included. The meta-analysis revealed a significant relationship between the high expression of SIRT1 and higher T-stage (odds ratio=2.39. 95% confidence interval=1.12-5.13, p=0.02), more advanced TNM stage (odds ratio=2.35. 95% confidence interval=1.20-4.60, p=0.01), and a poor overall survival (hazard ratio=1.90, 95% confidence interval=1.45-2.47, p<0.00001). Conclusion: SIRT1 expression may be a promising prognostic biomarker for patients with ESCC.

Metformin-Induced Heat Shock Protein Family A Member 6 Is a Promising Biomarker of Esophageal Squamous Cell Carcinoma.

INTRODUCTION: Antidiabetic drug metformin exerts various antitumor effects on different cancers. Esophageal squamous cell carcinoma (ESCC) is an intractable digestive organ cancer and new treatment strategy is required. In this study, we performed a comprehensive gene expression analysis of ESCC cell lines treated with metformin, which provided helpful information on the antitumor effects of metformin in ESCC. Next, we selected a promising gene among them and examined its effects on ESCC properties. METHODS: We examined metformin-induced mRNA expression changes in two human ESCC cell lines by performing next-generation sequencing (NGS) and pathway analysis. Heat shock protein family A (Hsp70) member 6 (HSPA6) expression in surgical specimens obtained from 83 ESCC patients who underwent curative operations was evaluated immunohistochemically and analyzed. RESULTS: Metformin upregulated mRNA expression of the many genes, including HSPA6, a cancer immune-related gene, and inhibited mRNA expression of the other many genes. Pathway analysis indicated major canonical pathways and upstream regulators related to metformin. The result indicated HSPA6 as a promising biomarker. HSPA6 expression correlated with disease-free survival (DFS) of the patients with all stage ESCC (p = 0.021), especially with stage I/II ESCC (p < 0.001). With stage III, low HSPA6 expression was not associated with poor DFS (p = 0.918). Multivariate analysis indicated that independent low HSPA6 expression was an independent poor prognostic factor of stage I/II ESCC (p < 0.001). However, HSPA6 expression did not correlate with the clinicopathological characteristics, including age, sex, tumor depth, lymph node metastasis, tumor stage, and tumor markers of the patients with stage I/II ESCC. CONCLUSIONS: This NGS analysis detected prospective candidate genes, including HSPA6. Our results indicate that HSPA6 is a promising biomarker of the recurrence risk of stage I/II ESCC. Further studies on HSPA6 would lead to better treatment.

Biased expression of mutant alleles in cancer-related genes in esophageal squamous cell carcinoma.

BACKGROUND: Recent progress of large-scale international studies has provided comprehensive catalogs of somatic mutations in cancers. Additionally, it has become evident that allelic imbalance in the abundance of somatic mutations between DNA and RNA were pervasive in various types of cancer. However, the allelic imbalance of the abundance of somatic mutations in esophageal squamous cell carcinoma (ESCC) has not been fully analyzed. METHODS: We performed exome sequencing for 25 Japanese patients with ESCC to detect a comprehensive catalog of somatic mutations in ESCC. Additionally, we performed mRNA sequencing to evaluate the allelic imbalance of the identified somatic mutations at the transcriptional level by comparing the mutant allele frequencies between RNA and DNA. RESULTS: The exome sequencing showed that TP53 and ZNF750 were significantly mutated genes. The expression levels of TP53 and ZNF750 were different depending on the mutation status. In almost all the tumors with missense mutations in TP53 and ZNF750, the mutant allele frequencies were higher in the RNA sequencing than those in the exome sequencing, indicating that the mutant alleles were preferentially expressed. By examining the allelic imbalances for all the identified missense mutations, we demonstrated that genes showing preferential expressions of the mutant alleles were involved in the pathways including cell cycle, cell death, and chromatin modification. CONCLUSIONS: The results of this study suggest that the allelic imbalance of the abundance of somatic mutations plays important roles in the initiation and progression of ESCC by modulating cancer-related biological pathways.

Soluble PD-L1 Concentration Is Proportional to the Expression of PD-L1 in Tissue and Is Associated with a Poor Prognosis in Esophageal Squamous Cell Carcinoma.

INTRODUCTION: We determined the soluble programmed cell death-1 ligand-1 (sPD-L1) concentration in patients with esophageal squamous cell carcinoma (ESCC), and confirmed the PD-L1 expression in resected specimens. METHODS: Blood samples were collected from 73 patients with histologically proven ESCC. The serum levels of sPD-L1 were measured using an enzyme-linked immunosorbent assay. The correlations between the sPD-L1 concentration and the expression of PD-L1 in tumor specimens and tumor depth, lymph node metastasis, disease stage, and various laboratory data were assessed. RESULTS: sPD-L1 levels in patients with high PD-L1 expression levels in tumor tissue were significantly higher than in patients with low PD-L1 expression levels (p = 0.042). The OS of the sPD-L1-high group was significantly worse than that of the low group (p = 0.028). Similarly, patients in whom a tissue specimen was PD-L1-positive group showed significantly poorer OS. CONCLUSION: The sPD-L1 concentration was correlated with the PD-L1 expression in tissues. Patients with PD-L1-positive tissue specimens showed significantly higher sPD-L1 levels in comparison to PD-L1-negative cases. Furthermore, patients with high sPD-L1 expression levels had a significantly worse prognosis than those with low sPD-L1 expression levels, and patients with a PD-L1-positive tissue specimen had a significantly worse prognosis than patients in whom the tissue specimen showed a low PD-L1 expression level.

Multicenter phase II clinical study of the efficiency and safety of capecitabine plus intermittent oxaliplatin with bevacizumab as first-line therapy in patients with metastatic colorectal cancer (VOICE trial).

PURPOSE: The aim of this phase II study was to evaluate the efficacy and safety of combination therapy with five-cycle CAPOX (capecitabine plus oxaliplatin) plus bevacizumab, followed by five-cycle maintenance therapy with capecitabine plus bevacizumab and reintroduction of CAPOX plus bevacizumab for five cycles, with a preplanned intermittent oxaliplatin strategy in metastatic colorectal cancer (mCRC). METHODS: Patients with untreated mCRC were administered CAPOX (130 mg/m2 oxaliplatin on day 1, 2000 mg/m2/day capecitabine on days 1-14, every 21 days) + bevacizumab (7.5 mg/kg) every 3 weeks for five cycles, maintenance treatment without oxaliplatin for five cycles, and CAPOX + bevacizumab reintroduction for five cycles or upon tumor progression. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were the time to treatment failure (TTF), overall survival, response rate (RR), and safety. RESULTS: Forty-seven patients who fulfilled the inclusion criteria were enrolled in the evaluation of efficacy and safety. Median PFS was 14.1 months (95% confidence interval [CI], 8.6-19.5), and median TTF was 12.3 months (95% CI, 10.3-14.3). The objective RRs were 51.1% (24/47) during induction therapy, 58.3% (21/36) during maintenance therapy, and 63.6% (14/22) during reintroduction therapy. The frequency of patients with neutropenia, diarrhea, peripheral sensory neuropathy, venous thromboembolism, or grade ≥ 3 allergic reactions was 2.1%. CONCLUSION: CAPOX plus bevacizumab therapy with a preplanned intermittent oxaliplatin strategy consisting of brief five-cycle induction therapy, five-cycle maintenance therapy with capecitabine plus bevacizumab, and five-cycle reintroduction therapy consisting of CAPOX plus bevacizumab is safe and effective for mCRC patients. TRIAL REGISTRATION: UMIN ID: 000,005,732, date of registration: June 7, 2011.  https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000006695.

[Successful Endoscopic Submucosal Dissection of Early Gastric Cancer after Ulcer Healing Associated with a Malignant Cycle-A Case Report].

A 79-year-old man was detected with anemia on medical examination and underwent gastroscopy at the previous hospital. Gastroscopy revealed a 15-mm ulcerative lesion(Type 0-Ⅱc plus Ⅲ)on the greater curvature of the upper gastric body. Tumor biopsy showed well-differentiated adenocarcinoma. The patient was suspected of deep submucosal invasion due to poor stretching of the gastric wall and the ulcer depth; hence, he was transferred to our hospital for surgery. When gastroscopy was repeated, the ulcer was found to be scarred(Type 0-Ⅱc), thereby indicating the occurrence of intramucosal carcinoma; hence, endoscopic submucosal dissection was performed. The pathological finding showed 10×6 mm, tub1, pT1a, ly0, v0, pUL1, pHM0, pVM0, suggesting a curative resection. Early gastric cancer of the depressed type is known to develop a malignant cycle with repeated improvements and exacerbations of the ulcer. Diagnosing the depth of tumor invasion is particularly difficult when there is an active ulcer. For small lesions with active ulcers, repeating gastroscopy might allow for correct diagnosis and appropriate treatment.

Magnetic compression anastomosis is effective in treating stenosis after esophageal cancer surgery: a case report.

BACKGROUND: Esophagostomy is important in the treatment of esophageal cancer. However, esophagectomy has a higher risk of postoperative complications. Treatment for complications is often difficult, and in some cases, oral intake is no longer possible. Recently, magnetic compression anastomosis (MCA) was developed; it is a relatively safe method of anastomosis that does not require surgery in patients with stricture, obstruction, or dehiscence of the anastomosis after surgery. CASE PRESENTATION: The patient was a 76-year-old Japanese man. He underwent esophagectomy with a three-field dissection for esophageal cancer. A cervical esophagostomy and chest drainage were performed for necrosis of the gastric tube. Following infection control, colon interposition was performed. However, after the operation, the colon necrotized and formed an abscess. Drainage controlled the infection, but the colon was completely obstructed. The patient was referred to our hospital to restore oral ingestion. Contrast studies showed that the length of the occlusion was 10 mm. The reconstruction was examined; reanastomosis by surgery was judged to be a high risk, so the strategy of anastomosis by MCA was adopted. In the operation, the anterior chest was opened to expose the colon, and a magnet was inserted directly into the blind end of the colon. The magnet was guided to the blind end of the esophagus using an oral endoscope. Two weeks after MCA, a contrast study confirmed the passage of the contrast agent from the esophagus to the colon. The patient eventually took 18 bougies after the MCA. However, since then, he has not needed a bougie. As of 1 year and 8 months after the MCA, the patient is living at home with oral intake restored. CONCLUSIONS: MCA is an effective and safe treatment for complete stenosis after esophageal cancer surgery.

Caspase recruitment domain family member 9 expression is a promising biomarker in esophageal squamous cell carcinoma.

AIM: Esophageal squamous cell carcinoma (ESCC) is a refractory digestive organ cancer that requires better treatment strategies. We have recently reported that the antidiabetic drug metformin exerts antitumor effects on ESCC by inhibition of nuclear factor kappa B (NF-κB) nuclear translocation. In the present study, we focused on caspase recruitment domain family member 9 (CARD9), an essential signal adapter in NF-κB activation to examine whether it can be used as a prognostic factor in ESCC. METHODS: We investigated CARD9 expression immunohistochemically in clinical samples obtained from 93 patients with ESCC who underwent curative esophagectomy. CARD9 expression was analyzed for correlation with clinicopathological characteristics and ESCC prognosis. The molecular effects were investigated by knocking down ESCC cells. Comprehensive RNA expression changes in these ESCC cells were detected by next-generation sequencing (NGS). RESULTS: High CARD9 expression is significantly correlated with advanced tumor depth (P < .001), positive lymph node metastasis (P = .005) and advanced stage (P = .001). Kaplan-Meier method and the log-rank test showed that overall survival (OS) and disease-free survival (DFS) were significantly poor in the high CARD9 expression group (OS: P = .027, DFS: P = .005). Univariate and multivariate analysis showed that high CARD9 expression is a significant poor prognostic factor for DFS. Cell proliferation and migration were suppressed by CARD9 knockdown. NGS detected altered the expression of some RNAs including maternally expressed 3 (MEG3). CONCLUSION: High CARD9 expression is significantly associated with poor prognosis. Therefore, CARD9 expression may be a prospective prognostic biomarker in ESCC.

[Development of TP53-Targeted Treatment in Esophageal Squamous Cell Carcinoma Using Cancer Genomic Profiling Test].

Recently, the interest in cancer genomic medicine has increased, owing to the powerful and cost-effective technology of next-generation sequencing(NGS), which allows rapid identification of a large number of gene mutations. TP53 mutations are frequently found in solid cancers, especially in esophageal squamous cell carcinoma(ESCC), wherein the frequency of TP53 mutation is considered to be 90% or more. However, there is no clinical targeted therapy as yet utilizing TP53. Here, we aimed to characterize TP53 mutations associated with ESCC, in order to assess its feasibility as a therapeutic target. We extracted DNA and RNA from specimens of ESCC patients and analyzed them using NGS, which revealed different TP53 mutations. Based on previous reports, it is considered that different TP53 mutations lead to different functions of the protein, and subsequently account for varied prognosis in squamous cell carcinoma of the head and neck. We also performed cell viability assay using ESCC cell lines with different TP53 mutations and 2 kinds of p53-targeted drug and found differences in the growth inhibition of the cell lines. Although individual treatment can be determined depending on the type of TP53 mutation, it would be necessary to further examine the interaction of TP53 with other genes to determine its therapeutic efficacy as a target.

[Successful Treatment of Gastric Cancer with Conversion Surgery after Nivolumab Treatment-A Case Report].

Immunocheckpoint inhibitors including anti-PD-1 antibody have shown certain therapeutic effects on various cancer types. They have also attracted great attention as novel cancer treatment options in addition to surgical resection, chemotherapy, and radiation therapy. Herein, we report a case of gastric cancer that was successfully treated with conversion surgery after nivolumab treatment. The patient was 68 years old and male. Upper gastrointestinal endoscopy revealed a type 3 tumor in the antrum, and he was referred to our department for further examination. The gastric cancer was diagnosed as cT4aN2M0, cStage ⅢA, and he was administered SOX as the first-line and nab-PTX/RAM as the second-line treatment, which was also a PD. As the third-line treatment, nivolumab showed remarkable reduction of the tumor after initiation, and after 14 courses, conversion surgery was performed. The patient remains alive without recurrence.

Short-term clinical outcomes of laparoscopic gastrectomy for remnant gastric cancer: A single-institution experience and systematic review of the literature.

AIM: Application of laparoscopic approaches for the treatment of remnant gastric cancers (RGC) is still controversial. Therefore, in the present study, the safety and effectiveness of laparoscopic gastrectomy (LG) for RGC was investigated. METHODS: A total of 27 patients who underwent gastrectomy for RGC from June 2008 to September 2017 were enrolled in this study. A comprehensive review of the literature on LG for RGC published before December 2017 using the PubMed database was carried out. RESULTS: Laparoscopic gastrectomy was carried out in seven patients, and open gastrectomy (OG) was done in the remaining 20 patients. LG was associated with significantly less intraoperative blood loss (70 ± 71 vs. 1066 ± 1428 g; P < 0.001), significantly more retrieved lymph nodes (22 ± 13 vs. 12 ± 9; P = 0.03), a relatively lower postoperative complication rate, and a relatively shorter postoperative hospital stay than OG. A comprehensive review of the literature showed that LG for RGC was more likely to correlate with longer operative time, less blood loss, lower postoperative complication rate, shorter postoperative hospital stay, and more retrieved lymph nodes than OG. CONCLUSION: The clinical outcome of our patients with RGC and the literature indicated that a laparoscopic approach contributed to faster recovery after surgery than an open approach without sacrificing its radicality and was a safe and secure treatment option for RGC.

Pharmacokinetics of cisplatin in an esophageal cancer patient on hemodialysis who was treated with a full-dose cisplatin-fluorouracil regimen: A case report.

INTRODUCTION: Cancer patients undergoing hemodialysis might be under-treated because the pharmacokinetics of anti-cancer drugs in such patients remain unknown and out of concern related to the potential development of severe adverse effects. However, patients with chemosensitive cancer, such as esophageal cancer, should receive chemotherapy at a dose that is sufficient to attain a favorable therapeutic effect. We herein present an interesting case involving an esophageal cancer patient who was successfully treated with subtotal thoracic esophagectomy, and adjuvant full-dose chemotherapy with cisplatin and 5-fluorouracil while concomitantly undergoing hemodialysis. We carried out a pharmacokinetics analysis of cisplatin, and also conducted a systematic review on the dose and pharmacokinetics. CASE REPORT: A 57-year-old male patient with esophageal cancer who was undergoing hemodialysis was referred to our hospital. He underwent subtotal thoracic esophagectomy. The pathological diagnosis was T1b, N2 (5/26), M0, ly2, v2, stage IIIA (Union for International Cancer Control, 8th edition). Because of the high degree of lymph node metastasis, adjuvant chemotherapy with cisplatin was recommended. Cisplatin (80 mg/m2) was infused intravenously within 30 min on day 1, and 5-fluorouracil (800 mg/m2) was infused continuously on days 1-5 of a 28-day cycle. Thrombocytopenia (grade 3) occurred on day 16, leucopenia (grade 3) occurred on day 23, and anemia (grade 3) occurred on day 30. The onset of hematologic toxicities was prolonged in comparison to patients with a normal renal function.

The Antitumor Effects of Metformin on Gastric Cancer In Vitro and on Peritoneal Metastasis.

BACKGROUND/AIM: Gastric cancer (GC) with peritoneal metastasis remains difficult to treat. The anti-diabetic drug metformin exerts various antitumor effects via the 5'-adenosine monophosphate-activated protein kinase (AMPK) pathway and nuclear factor-kappa B (NF-ĸB). Therefore, we evaluated the antitumor effects of metformin for GC in vitro and on peritoneal metastasis. MATERIALS AND METHODS: The human GC cell lines MKN1, MKN45, KATO-III and SNU-1 were used. The antiproliferative effect was evaluated in vitro with 0.5 mM or 25 mM glucose and in vivo using tumor xenograft peritoneal models of metastasis. The protein expression of AMPK, liver kinase B1 (LKB1) and NF-ĸB in tumors was examined by western blotting. RESULTS: Metformin inhibited cell proliferation in all GC lines and sensitivity was increased under low-glucose conditions in vitro. Metformin also suppressed peritoneal metastasis. In tumors, metformin reduced the numbers of proliferating cells and NF-ĸB expression, but a similar trend was not noted for AMPK. CONCLUSION: Metformin may be a useful drug for the treatment of GC with peritoneal metastasis.

Antitumor effects of metformin are a result of inhibiting nuclear factor kappa B nuclear translocation in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is an intractable digestive organ cancer that has proven difficult to treat despite multidisciplinary therapy, and a new treatment strategy is demanded. Metformin is used for type 2 diabetes mellitus and its antitumor effects have been reported recently. Metformin exerts antitumor effects in various respects, such as inhibiting inflammation, tumor growth and epithelial-mesenchymal transition (EMT). However, few reports have described the efficacy of metformin on ESCC, and their findings have been controversial. We analyzed the antitumor effects of metformin and clarified its effects on anti-inflammation, growth suppression and EMT inhibition. Activation of nuclear factor kappa B (NF-κB), the major transcription factor induced by inflammation, was investigated by immunostaining. We found that localization of NF-κB in the nucleus was reduced after metformin treatment. This suggests that metformin inhibited the activation of NF-κB. Metformin inhibited tumor growth and induced apoptosis in ESCC cell lines. Associated with EMT, we examined cell motility by a wound healing assay and the epithelial marker E-cadherin expression of various ESCC cell lines by western blotting. Metformin inhibited cell motility and induced E-cadherin expression. In conclusion, metformin showed multiple antitumor effects such as growth suppression, invasion inhibition, and control of EMT by inhibiting NF-κB localization on ESCC. Further exploration of the marker of treatment efficacy and combination therapy could result in the possibility for novel treatment to use metformin on ESCC.

ZNF750 Expression Is a Potential Prognostic Biomarker in Esophageal Squamous Cell Carcinoma.

OBJECTIVE: ZNF750, a transcriptional regulator of epidermal differentiation, has been identified as a tumor suppressor in esophageal squamous cell carcinoma (ESCC). The aim of the present study was to investigate the clinical and prognostic significance of ZNF750 expression and to evaluate the effect of ZNF750 knockdown on cell proliferation, migration, and invasion in ESCC. METHODS: A total of 124 patients with ESCC who underwent curative esophagectomy were evaluated in this study. The expression of ZNF750 in surgical specimens was immunohistochemically assessed and used in the analysis of clinicopathological features and overall survival (OS). The molecular role of ZNF750 was investigated by ZNF750 knockdown using small interfering RNA (siRNA) in ESCC cell lines. RESULTS: Low ZNF750 expression had a significant correlation with positive lymph node metastasis (p = 0.028). Furthermore, there was a significant relationship between low expression of ZNF750 in ESCC and a poor OS, and a multivariate analysis showed that low ZNF750 expression was an independent prognostic factor (p = 0.020). The cell growth, migration, and invasion were significantly increased by downregulation of ZNF750. CONCLUSIONS: The low expression of ZNF750 was significantly associated with a poor prognosis, and ZNF750 expression may, therefore, be a reliable prognostic biomarker in ESCC.

ZNF750 Expression as a Novel Candidate Biomarker of Chemoradiosensitivity in Esophageal Squamous Cell Carcinoma.

OBJECTIVE: ZNF750, an epidermal differentiation regulator, has been suggested to act as a tumor suppressor of esophageal squamous cell carcinoma (ESCC). Although a correlation between the epidermal differentiation gene and resistance to chemoradiotherapy (CRT) has been posited, no data regarding the ZNF750 status in ESCC have been reported. The aim of the present study was to evaluate the relationship between ZNF750 expression and response to CRT in ESCC. METHODS: Eighty-seven patients who had been pathologically diagnosed with ESCC were evaluated in the present study. All patients underwent neoadjuvant CRT, followed by curative esophagectomy. The expression of ZNF750 in pretreatment biopsy samples was immunohistochemically investigated and compared to the histopathological effectiveness of CRT in surgical specimens. RESULTS: High expression of ZNF750 was closely correlated with good sensitivity to CRT (p = 0.016). A univariate analysis showed that high/intermediate expression of ZNF750 was a significant predictive factor for good sensitivity to CRT (p = 0.006). High/intermediate expression of ZNF750 (30% or more) remained an independent predictive factor for sensitivity to CRT in a multivariate analysis (p = 0.033). CONCLUSIONS: ZNF750 expression predicts sensitivity to CRT and can be a biomarker that reliably predicts the response of ESCC to CRT.

Diffusely infiltrative squamous cell carcinoma of the esophagus presenting as a case with diagnostic difficulty.

We report a rare case of diffusely infiltrative squamous cell carcinoma of the esophagus. The patient, a 68-year-old man, was admitted to our hospital for investigation of dysphagia. Esophagography and upper gastrointestinal endoscopy revealed esophageal stenosis and gastric cancer. As a biopsy from the esophagus revealed no sign of malignancy, he underwent only distal gastrectomy. After 3 months, the stenosis became worse. Again, biopsy from a gastrointestinal endoscopy showed no malignancy, but endobronchial ultrasound-guided transbronchial needle aspiration revealed squamous cell carcinoma of the esophagus. Despite various treatments, the patient died of disease progression 20 months after its onset. Autopsy revealed diffusely infiltrative squamous cell carcinoma of the esophagus, which is a rare malignancy with few case reports documented.

The molecular role of Fra-1 and its prognostic significance in human esophageal squamous cell carcinoma.

BACKGROUND: The expression of Fra-1 (Fos related antigen 1) involves tumor progression and invasion, and its gene ablation could suppress the invasive phenotypes of human tumor cells. The authors investigated the significance of Fra-1 expression in esophageal squamous cell carcinoma (ESCC) and studied the effect of its down-regulation on cell proliferation, motility, and invasion. METHODS: Surgical specimens from 164 patients with ESCC were evaluated. Fra-1 expression in the primary tumor along with metastatic lymph nodes was compared among various clinicopathological characteristics, and overall survival was analyzed. The rate and intensity of Fra-1 immunoreactivity were also investigated. The molecular role of Fra-1 was assessed by its down-regulation in human ESCC cell lines. RESULTS: Fra-1 expression was positive in 127 (77.4%) ESCC patients. Immunoreactivity was localized to the marginal areas of the ESCC tumors. Positive Fra-1 expression correlated with depth of tumor, lymph node metastasis, stage, and infiltrative growth pattern. A significant difference was seen in the survival between tumors with and without Fra-1, and positive Fra-1 expression was revealed to be an independent factor related to poor prognosis. Patients with metastatic lymph nodes with positive Fra-1 expression presented decreased survival compared with negative Fra-1 expression. After the down-regulation of Fra-1 expression, a significant decrease in cell proliferation, motility, and invasion was observed. CONCLUSIONS: This study demonstrated ESCC patients positive for Fra-1 to be associated with poor prognosis. The findings also suggest that Fra-1 regulation may play an important role in the progression of ESCC.