Overexpression of alternative splicing of far upstream element binding protein 1 (FUBP1) interacting repressor (FIR; poly(U) binding splicing factor 60 [PUF60]) and cyclin E were detected in esophageal squamous cell carcinomas (ESCC). Accordingly, the expression of FBW7 was examined by which cyclin E is degraded as a substrate via the proteasome system. Expectedly, FBW7 expression was decreased significantly in ESCC. Conversely, c-myc gene transcriptional repressor FIR (alias PUF60; U2AF-related protein) and its alternative splicing variant form (FIRΔexon2) were overexpressed in ESCC. Further, anticancer drugs (cis-diaminedichloroplatinum/cisplatin [CDDP] or 5-fluorouracil [5-FU]) and knockdown of FIR by small interfering RNA (siRNA) increased cyclin E while knockdown of FIRΔexon2 by siRNA decreased cyclin E expression in ESCC cell lines (TE1, TE2, and T.Tn) or cervical SCC cells (HeLa cells). Especially, knockdown of SAP155 (SF3b1), a splicing factor required for proper alternative splicing of FIR pre-mRNA, decreased cyclin E. Therefore, disturbed alternative splicing of FIR generated FIR/FIRΔexon2 with cyclin E overexpression in esophageal cancers, indicating that SAP155 siRNA potentially rescued FBW7 function by reducing expression of FIR and/or FIRΔexon2. Remarkably, Three-dimensional structure analysis revealed the hypothetical inhibitory mechanism of FBW7 function by FIR/FIRΔexon2, a novel mechanism of cyclin E overexpression by FIR/FIRΔexon2-FBW7 interaction was discussed. Clinically, elevated FIR expression potentially is an indicator of the number of lymph metastases and anti-FIR/FIRΔexon2 antibodies in sera as cancer diagnosis, indicating chemical inhibitors of FIR/FIRΔexon2-FBW7 interaction could be potential candidate drugs for cancer therapy. In conclusion, elevated cyclin E expression was, in part, induced owing to potential FIR/FIRΔexon2–FBW7 interaction in ESCC.
Esophageal lymphoepithelioma-like carcinoma (LELC) is extremely rare. We report the first case of esophageal LELC showing macroscopic reduction. A 67-year-old male presented with dysphagia and, by endoscopic examination, was found to have a significantly raised tumor of 10 mm in diameter in the thoracic esophagus. The biopsied material showed esophageal cancer. We performed endoscopic submucosal dissection. However, the tumor became flattened, similar to a scar, in only 2 mo. Histologically, the carcinoma cells had infiltrated the submucosal layer. Prominent infiltration of T lymphoid cells that stained positive for CD8 was observed around the carcinoma cells. Therefore, this lesion was considered to be an LELC with poorly differentiated squamous cells. Because the margin was positive, an esophagectomy was performed. Carcinoma cells were detected in the neck in one lymph node. The staging was T1N0M1b. However, the patient has been well, without adjuvant therapy or recurrence, for more than 5 years.
Background and aimsEUS-guided FNA biopsy has been widely performed to aid in the diagnosis of submucosal tumors (SMTs). However, in cases of small tumors, the diagnostic yield of EUS-FNA is poor. Therefore, it is necessary to develop a new needle for the diagnosis. We developed a device with a new mechanism that we refer to as a drill needle aspiration biopsy (DNAB). The aim of this study was to evaluate the use of DNAB in resected gastric SMT specimens.MethodsA drill needle with a sharp tip and wide ditch was inserted into a catheter for angiography. Continuous suction is enabled through the catheter at the tip. DNAB was performed with one pass and one stroke in 13 gastric SMTs resected by operation. Similarly, FNA was performed by one pass and ten strokes. These gastric tumors included nine diagnosed gastrointestinal stromal tumors and four undiagnosed SMTs by preoperative examinations. The tissue quantity between DNAB and FNA was macroscopically and microscopically examined.ResultsAll 13 drill biopsy specimens were obtained. Additionally, all 13 gastric SMTs, including 4 undiagnosed tumors, could be diagnosed by DNAB. The quantity of each specimen obtained by DNAB was macroscopically and microscopically much greater than that by FNA. In particular, for tumors <25 mm in the longer axis, the ratio of microscopic diagnosable cases was 100 % (7/7) for DNAB and 42.9 % (3/7) for FNA.ConclusionsDNAB is a novel method that can obtain more tissue than FNA for small gastric SMT.
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