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Akihiko Sano,
Shinji Sakurai,
Hiroyuki Kato,
Shigemasa Suzuki,
Takehiko Yokobori,
Makoto Sakai,
Naritaka Tanaka,
Takanori Inose,
Makoto Sohda,
Masanobu Nakajima,
Yasuyuki Fukai,
Tatsuya Miyazaki,
Hitoshi Ojima,
Yoshinori Hosoya,
Takehiko Enomoto,
Tatsuo Kanda,
Yoichi Ajioka,
Hiroyuki Kuwano
[show abstract]
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ABSTRACT: Esophageal carcinosarcoma (ECS) is a rare malignant neoplasm associated with a poor patient prognosis. It is characterized by the presence of both malignant epithelial and mesenchymal components. Molecular-targeted therapy of several receptor tyrosine kinases (RTKs) has been reported to be effective in the treatment of various malignant tumors, including carcinosarcoma of several organs. This study aimed to assess the therapeutic potential of targeting RTKs in ECS. Overexpression of RTKs was assessed in 21 ECS cases by immunohistochemistry (IHC). Positively stained cases were further examined for RTK gene mutations and amplifications by direct sequencing analysis and fluorescence in situ hybridization. In epithelial components, KIT, platelet-derived growth factor receptor (PDGFR)A, PDGFRB, MET, epidermal growth factor receptor (EGFR) and HER-2 were overexpressed in 1 (4.8%), 1 (4.8%), 0 (0%), 11 (52.4%), 13 (61.9%) and 2 (9.5%) cases, respectively. In the mesenchymal components the corresponding numbers of cases were 2 (9.5%), 2 (9.5%), 0 (0%), 12 (57.1%), 11 (52.4%) and 0 (0%). No mutations in the c-kit, PDGFRA and c-met genes were found. Among 19 EGFR-positive tumors, 2 had EGFR missense mutations (T790A, exon 20) only in the mesenchymal component. Gene amplification or high polysomy of c-kit, PDGFRA, c-met and EGFR was observed in 1 (33.3%), 0 (0%), 3 (18.8%) and 10 (52.6%) cases, respectively. In conclusion, various RTKs, particularly MET and EGFR were overexpressed in ECSs suggesting that molecular-targeted therapies directed to MET, EGFR or other RTKs may be effective in inhibiting the growth or progression of the epithelial and/or mesenchymal component of ECS.
Oncology Reports 03/2013; · 1.84 Impact Factor
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Tatsuya Miyazaki,
Makoto Sohda,
Naritaka Tanaka,
Shigemasa Suzuki,
Keisuke Ieta,
Makoto Sakai, Akihiko Sano,
Takehiko Yokobori,
Takanori Inose,
Masanobu Nakajima,
Minoru Fukuchi,
Hitoshi Ojima,
Hiroyuki Kato,
Hiroyuki Kuwano
[show abstract]
[hide abstract]
ABSTRACT: More effective protocols are needed for unresectable and recurrent esophageal cancer. Therefore, we conducted a phase I trial to establish the recommended dose of docetaxel, nedaplatin, and 5-fluorouracil (DNF) as combination chemotherapy. Fourteen patients with esophageal cancer were enrolled and received DNF combination therapy at different dose levels according to the treatment and examination plan. Dose-limiting toxicities (DLTs) included febrile neutropenia. DLTs occurred in 3/5 patients at level 4. The recommended doses (level 3) of DNF were 60 mg/m(2) (day 1), 70 mg/m(2) (day 1), and 700 mg/m(2) (days 1-5), respectively, given at 3-week intervals. In conclusion, DNF combined chemotherapy for advanced esophageal cancer was associated with relatively minor adverse events and was safely administered at the recommended dose. A phase II study is now underway.
Cancer Chemotherapy and Pharmacology 01/2013; · 2.83 Impact Factor
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Takehiko Yokobori,
Shigemasa Suzuki,
Naritaka Tanaka,
Takanori Inose,
Makoto Sohda, Akihiko Sano,
Makoto Sakai,
Masanobu Nakajima,
Tatsuya Miyazaki,
Hiroyuki Kato,
Hiroyuki Kuwano
Cancer Science 01/2013; 104(1):Januarycover. · 3.33 Impact Factor
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Takanori Inose,
Tatsuya Miyazaki,
Shigemasa Suzuki,
Naritaka Tanaka,
Makoto Sakai, Akihiko Sano,
Takehiko Yokobori,
Makoto Sohda,
Masanobu Nakajima,
Minoru Fukuchi,
Hiroyuki Kato,
Hiroyuki Kuwano
[show abstract]
[hide abstract]
ABSTRACT: PURPOSE: Nonspecific esophageal motility disorder (NEMD) is a vague category that includes patients with poorly defined contraction abnormalities observed during esophageal manometry. This study investigated the therapeutic effects of the video-assisted thoracoscopic surgery (VATS) approach using long myotomy and fundopexy for NEMD. METHODS: The VATS approach using myotomy and fundopexy was performed for 4 patients of NEMD between 2005 and 2008. A total of 4 patients with NEMD that underwent treatment at our institution were analyzed retrospectively. RESULTS: The patients included 2 males and 2 females with a median age of 48 years (range 21-74 years). The median duration of NEMD symptoms was 58 months (range 4-108 months). Dysphagia was a primary symptom in all patients. Chest pain was a primary symptom in 3 of 4 patients (75 %). Treatment with medication was attempted before the operation. The median operative time was 344.5 min (range 210-476 min). The median time before starting oral feeding was 2.5 days (range 2-22 days). All patients achieved a significant improvement of their previous condition. CONCLUSIONS: The VATS approach using myotomy and fundopexy for NEMD is a good treatment in cases resistant to medication and balloon dilation.
Surgery Today 12/2012; · 1.22 Impact Factor
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Takehiko Yokobori,
Shigemasa Suzuki,
Naritaka Tanaka,
Takanori Inose,
Makoto Sohda, Akihiko Sano,
Makoto Sakai,
Masanobu Nakajima,
Tatsuya Miyazaki,
Hiroyuki Kato,
Hiroyuki Kuwano
[show abstract]
[hide abstract]
ABSTRACT: The association of microRNAs (miRs) with cancer progression has been established in many cancers including esophageal squamous cell carcinoma (ESCC). A public microarray database showed that the expression of miR-150 was lower in ESCC than in normal esophageal mucosa. Here, we focused on ZEB1, epithelial-mesenchymal-transition (EMT)-inducers, as target genes of miR-150 based on in silico predictions. The purpose of this study was to clarify the clinicopathological significance of miR-150 in ESCC, and to investigate miR-150's EMT-regulatory ability. Quantitative RT-PCR was used to evaluate miR-150 expression in 108 curative resected ESCC samples to determine the clinicopathological significance. Moreover, we examined the in vitro and in vivo function of miR-150 via degradation of ZEB1. MiR-150 expression was significantly lower in cancer tissues compared to adjacent non-cancerous tissues (p<0.001). Low expression of miR-150 in ESCC contributed to malignant potential, such as tumor depth, lymph node metastasis, lymphatic invasion, venous invasion, clinical staging, and poor prognosis (p<0.05). In vitro assays showed that EMT-inducer-ZEB1 is a new direct target of miR-150. Moreover, miR-150 induced MET-like changes in TE-8 cells through ZEB1 degradation (e.g., E-cadherin expression, vimentin repression, epithelial morphology, and suppression of migration ability), and significantly inhibited tumorigenicity and tumor growth in a mouse xenograft model. Analysis of the regulation of ZEB1 by miR-150 could provide new insights into preventing metastasis and also suggests novel targeted therapeutic strategies in ESCC.
Cancer Science 09/2012; · 3.33 Impact Factor
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Shigemasa Suzuki,
Takehiko Yokobori,
Naritaka Tanaka,
Makoto Sakai, Akihiko Sano,
Takanori Inose,
Makoto Sohda,
Masanobu Nakajima,
Tatsuya Miyazaki,
Hiroyuki Kato,
Hiroyuki Kuwano
[show abstract]
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ABSTRACT: CD47 inhibits phagocytosis and its overexpression is correlated with poor prognosis in patients with several types of cancer. It has also been reported that CD47 expression in multiple sclerosis is regulated by microRNAs. However, the regulatory mechanism of CD47 in cancer tissues has not been yet clarified. Re-analysis of a public microarray database revealed that miR-133a is downregulated in esophageal squamous cell carcinoma (ESCC). Moreover, in silico algorithms predicted that miR-133a is a regulator of CD47. The purpose of this study was to clarify the clinical significance of CD47 and its regulatory mechanism by miR-133a in ESCC. Quantitative real-time RT-PCR was used to evaluate CD47 and miR-133a expression in 102 cases of curative resected ESCC and adjacent non-cancerous tissue. The regulation of CD47 by miR-133a was examined with precursor miR-133a-transfected cells. A mouse xenograft model was used to investigate the ability of miR-133a to suppress tumor progression. High expression levels of CD47 were associated with lymph node metastasis (P=0.049). Multivariate analysis showed that CD47 expression was an independent prognostic factor (P=0.045). miR-133a expression was significantly lower in cancer tissues compared to adjacent non-cancerous tissues (P<0.001). In vitro assays showed that miR-133a is a direct regulator of CD47. miR‑133a significantly inhibited tumorigenesis and growth in vivo. CD47 expression is a novel prognostic marker in ESCC that is directly inhibited by the miR-133a tumor suppressor. This correlation could provide new insight into the mechanism of cancer progression and a promising candidate for target therapy in ESCC.
Oncology Reports 05/2012; 28(2):465-72. · 1.84 Impact Factor
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ABSTRACT: Extranodal invasion (ENI) has been reported to be associated with a poor prognosis in several malignancies. However, previous studies have included perinodal fat tissue tumor deposits in their definitions of ENI. To investigate the precise nature of ENI in esophageal squamous cell carcinoma (ESCC), we excluded these tumor deposits from our definition of ENI and defined tumor cell invasion through the lymph node capsule and into the perinodal tissues as lymph node capsular invasion (LNCI). The aim of the current study was to elucidate the significance of LNCI in ESCC.
We investigated the associations between LNCI and other clinicopathologic features in 139 surgically resected ESCC. We also investigated the prognostic significance of LNCI in ESCC.
LNCI was detected in 35 (25.2%) of 139 patients. The overall survival rate of the ESCC patients with LNCI was significantly lower than that of the ESCC patients with lymph node metastasis who were negative for LNCI. The survival difference between the patients with 1–3 lymph node metastases without LNCI and those with no lymph node metastasis was not significant. LNCI was significantly associated with distant organ recurrence. LNCI was also found to be an independent predictor of overall survival in addition to the number of lymph node metastases.
LNCI in ESCC patients is an indicator of distant organ recurrence and a worse prognosis. LNCI could be used as a candidate marker for designing more precise staging and therapeutic strategies for ESCC.
Annals of Surgical Oncology 01/2012; 19(6):1911-7. · 4.17 Impact Factor
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ABSTRACT: We report two cases of rectal malignant melanomas. The patients were an 84-year-old male and a 66-year-old female who had blood in their stools. They were preoperatively diagnosed with poorly differentiated adenocarcinoma of the rectum. The clinical diagnosis for each was rectal carcinoma at stage IIIc according to the tumor-node-metastasis classification (6th edition), and the patients underwent abdominoperineal resection with dissection of lymph nodes. Pathological examination of the resected specimens revealed a malignant melanoma. Immunohistochemical analysis results were positive for HMB-45 and negative for cytokeratin AE1/AE3, CD45, and synaptophysin. Primary anorectal melanoma is an uncommon and aggressive disease that carries a poor prognosis. Therefore, it is necessary to provide systemic treatment. To improve prognosis, it is important to detect anorectal melanoma at an early stage.
Case reports in surgery. 01/2012; 2012:247348.
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Masanobu Nakajima,
Hiroyuki Kato,
Tatsuya Miyazaki,
Minoru Fukuchi,
Norihiro Masuda,
Yasuyuki Fukai,
Makoto Sohda,
Takanori Inose,
Makoto Sakai, Akihiko Sano,
Naritaka Tanaka,
Faried Ahmad,
Hiroyuki Kuwano
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[hide abstract]
ABSTRACT: Heat shock proteins (HSPs) are well known as tumor rejection antigens, most notable of which is HSP70. HSP110 is classified as a member of the HSP70/DnaK superfamily. The objective of this study was to clarify the clinicopathological and prognostic significance of Heat Shock Protein 110 expression and T lymphocyte infiltration in esophageal cancer.
Immunohistochemical staining of HSP110, CD4 and CD8 were performed on surgical specimens obtained from 124 patients with esophageal cancer.
The expression of HSP110 correlated inversely with depth of invasion (p<0.0001), lymph node metastasis (p=0.0163), pathological stage (p<0.0001), lymphatic invasion (p=0.0104), blood vessel invasion (p=0.0027), infiltrative growth pattern (p=0.0368) and correlated positively with CD4+ T lymphocyte infiltration (p=0.0018). Reduction of HSP110 expression was significantly correlated with poor prognosis (p=0.0010).
The present findings suggest that HSP110 expression and T lymphocyte infiltration is a significant prognostic factor for esophageal cancer.
Hepato-gastroenterology 11/2011; 58(110-111):1555-60. · 0.66 Impact Factor
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Tatsuya Miyazaki,
Naritaka Tanaka,
Hanako Hirai,
Takehiko Yokobori, Akihiko Sano,
Makoto Sakai,
Takanori Inose,
Makoto Sohda,
Masanobu Nakajima,
Minoru Fukuchi,
Hiroyuki Kato,
Hiroyuki Kuwano
[show abstract]
[hide abstract]
ABSTRACT: Ghrelin is a peptide hormone predominantly produced by endocrine cells in the oxyntic mucosa of the stomach and is an endogenous ligand for the growth hormone secretagogue receptor. Ghrelin plays an important role in regulating appetite, food intake, and energy metabolism. We investigated the correlation between clinicopathologic factors and plasma ghrelin concentration before and after esophagectomy with gastric tube reconstruction for esophageal cancer treatment.
The study group comprised 25 patients (22 men, three women, age range 46-78 y) with esophageal cancer who underwent esophagectomy with gastric tube reconstruction between 1999 and 2007. Blood samples were collected before and three times after the operation. Plasma concentrations of ghrelin were determined using a sandwich-type enzyme immunoassay kit.
Plasma ghrelin concentrations were significantly decreased to 38.7% of the preoperative concentration at postoperative d 7. Plasma ghrelin concentrations recovered slightly over 6-24 mo postoperatively. After 36 mo or longer, ghrelin concentrations had returned to preoperative levels. There was no relationship between ghrelin concentrations and gender, location of tumor, tumor stage, operative procedure, and reconstruction route at each time point. There was a significant relationship between the decrease in body mass index and decrease in plasma ghrelin in patients at 6-24 mo after esophagectomy (P < 0.01).
Plasma ghrelin concentrations decrease on a temporary basis after esophagectomy with gastric tube reconstruction and are associated with body weight loss after surgery.
Journal of Surgical Research 10/2011; 176(1):74-8. · 2.25 Impact Factor
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Tetsuro Ohno,
Kyoichi Ogata,
Norimichi Kogure,
Hiroyuki Ando,
Ryuusuke Aihara,
Erito Mochiki,
Hiroaki Zai, Akihiko Sano,
Toshihide Kato,
Shinji Sakurai,
Tetsunari Oyama,
Takayuki Asao,
Hiroyuki Kuwano
[show abstract]
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ABSTRACT: Schwannomas are tumors originating from any nerve that has a Schwann cell sheath. Gastrointestinal (GI) schwannomas represent only 3% of all GI mesenchymal tumors. The stomach is the most common site of GI schwannomas, and schwannomas account for 0.2% of all gastric neoplasms. This report presents two cases of gastric schwannomas showing increased [18F]fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET; maximum standardized uptake value 7.10 and 6.05). Additional immunohistochemical staining of glucose transporter type 1 (GLUT1) and the autocrine motility factor (AMF) was conducted after the tumors were resected, to identify the mechanism that increased FDG uptake on PET. Immunohistochemical expression of AMF was positive in both cases, whereas GLUT1 was negative. Autocrine motility factor is also known as phosphoglucose isomerase. However, the mechanism by which FDG is accumulated in schwannoma cells is uncertain, and may be related to intracellular glycolytic activity.
Surgery Today 08/2011; 41(8):1133-7. · 1.22 Impact Factor
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Makoto Sohda,
Hiroyuki Kato,
Shigemasa Suzuki,
Naritaka Tanaka, Akihiko Sano,
Makoto Sakai,
Takanori Inose,
Masanobu Nakajima,
Tatsuya Miyazaki,
Minoru Fukuchi,
Noboru Oriuchi,
Keigo Endo,
Hiroyuki Kuwano
[show abstract]
[hide abstract]
ABSTRACT: The role and potential usefulness of positron emission tomography (PET) scanning in certain tumors has been widely investigated in recent years. (18)F-FAMT (L-[3-(18)F]-α-methyltyrosine) is an amino acid tracer for PET. This study investigated whether PET/CT with (18)F-FAMT provides additional information for preoperative diagnostic workup of esophageal squamous cell carcinoma compared with that obtained by (18)F-FDG (fluorodeoxyglucose) PET or CT.
PET/CT studies with (18)F-FAMT and (18)F-FDG were performed as a part of the preoperative workup in 21 patients with histologically confirmed esophageal squamous cell carcinoma.
For the detection of primary esophageal cancer, (18)F-FAMT-PET exhibited a sensitivity of 76.2%, whereas the sensitivity for (18)F-FDG-PET was 90.5% (P = 0.214). (18)F-FAMT uptake in primary tumors showed significant correlation with depth of invasion (P = 0.005), lymph node metastasis (P = 0.045), stage (P = 0.031), and lymphatic invasion (P = 0.029). In the evaluation of individual lymph node groups, (18)F-FAMT-PET exhibited 18.2% sensitivity, 100% specificity, 71.9% accuracy, 100% positive predictive value, and 70.0% negative predictive value, compared with 24.2%, 93.7%, 69.8%, 66.6%, and 70.2%, respectively, for (18)F FDG-PET. CT exhibited 39.4% sensitivity, 85.7% specificity, 69.8% accuracy, 59.1% positive predictive value, and 73.0% negative predictive value. The specificity of (18)F-FAMT-PET is significantly higher than that of (18)F-FDG-PET (P = 0.042) and CT (P = 0.002). (18)F-FAMT-PET did not have any false-positive findings compared to those with (18)F-FDG-PET.
Our findings suggest that the addition of (18)F-FAMT-PET to (18)F-FDG-PET and CT would permit more precise staging of esophageal cancer.
Annals of Surgical Oncology 12/2010; 17(12):3181-6. · 4.17 Impact Factor
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ABSTRACT: CD151 is a member of the tetraspanins and has recently been reported as a promoter of the malignant progression of cancer. The purpose of this study was to clarify the clinicopathological outcome and prognostic significance of the immunohistochemical expression of CD151 in esophageal squamous cell carcinoma (ESCC).
We evaluated the significance of CD151 expression by immunohistochemistry in 138 surgically resected ESCC and the association of CD151 expression with clinicopathological features.
Seventy-five (51.7%) ESCC showed a positive expression of CD151, which indicated a significant association with tumor depth (P = 0.004), lymph node metastasis (P = 0.002), distant metastasis (P = 0.025), and lymphatic invasion (P = 0.046), as well as the Ki-67 labeling index (P = 0.011). The 5-year survival rate of ESCC patients with CD151-positive expression was significantly lower than with CD151-negative expression (positive, 43.1%; negative, 63.8%; P = 0.003). Multivariate analysis showed that positive CD151 expression was not an independent factor for poor survival (P = 0.096).
CD151 expression is associated with tumor proliferation and invasiveness in ESCC.
Annals of Surgical Oncology 10/2010; 18(3):888-93. · 4.17 Impact Factor
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ABSTRACT: Karyopherin-alpha 2 (KPNA2) is a member of the importin alpha family and has recently been reported to play an important role in tumorigenesis and tumor progression. The aim of the current study was to elucidate the clinicopathological significance of immunohistochemical expression of KPNA2 in esophageal squamous cell carcinoma (ESCC).
KPNA2 expression was investigated by immunohistochemistry in 116 surgically resected ESCC, and the association of KPNA2 expression with clinicopathologic features was also examined.
Sixty (51.7%) ESCCs demonstrated positive expression of KPNA2. Positive expression of KPNA2 showed a significant association with poor differentiation (p=0.015), tumor depth (p=0.001), lymphatic invasion (p<0.001), venous invasion (p<0.001), and tumor stage (p=0.008). Positive expression of KPNA2 was also significantly associated with Ki-67 labeling index (p=0.039). Univariate analysis revealed that the prognosis of the ESCC patients whose tumors demonstrated positive expression of KPNA2 was significantly poorer than that of those that did not (p=0.009). Multivariate analysis revealed that only tumor depth and the presence of lymph node metastasis, which are strong prognostic factors in ESCC, were independently associated with poor prognosis in this study.
KPNA2 expression is associated with poor differentiation, tumor invasiveness, and tumor proliferation in ESCC.
Anticancer research 03/2010; 30(3):851-6. · 1.73 Impact Factor
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Naritaka Tanaka,
Hitoshi Kimura,
Ahmad Faried,
Makoto Sakai, Akihiko Sano,
Takanori Inose,
Makoto Sohda,
Koji Okada,
Masanobu Nakajima,
Tatsuya Miyazaki,
Minoru Fukuchi,
Hiroyuki Kato,
Takayuki Asao,
Hiroyuki Kuwano,
Takahiro Satoh,
Masakazu Oikawa,
Tomihiro Kamiya,
Kazuo Arakawa
[show abstract]
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ABSTRACT: Cisplatin is a key chemotherapeutic agent for the treatment of esophageal cancer. We examined the intracellular localization of cisplatin in esophageal cancer cell lines and determined their sensitivity to cisplatin using in-air micro-PIXE (particle induced X-ray emission). Two human esophageal squamous cell carcinoma (ESCC) cell lines, TE-2 and TE-13, were examined for their response to cisplatin using MTT assay, flow cytometry, and DNA fragmentation assays. Real-time reverse transcription-polymerase chain reaction was also used to evaluate the mRNA expression of multidrug resistance protein 2 (MRP2) in both cell lines. Platinum localizations of intracellular and intranuclear were measured using in-air micro-PIXE. TE-2 cells were more sensitive to cisplatin than TE-13 cells (IC(50): 37.5 mum and 56.3 mum, respectively). Flow cytometry analysis confirmed that more TE-2 than TE-13 cells were in the sub-G1 phase. DNA fragmentation assay was analyzed to confirm the MTT assay and flow cytometry results. The expression of MRP2 mRNA in TE-13 cells was stronger than in TE-2 cells. In-air micro-PIXE showed that TE-2 cells had higher intracellular cisplatin concentrations than TE-13 cells and the ratio of intranuclear to intracellular cisplatin in individual cells was not significantly different. We observed the intracellular and intranuclear localization of cisplatin using in-air micro-PIXE. The results of this study suggest that in-air micro-PIXE could be a useful quantitative method for evaluating the cisplatin sensitivity of individual cells. Finally, we speculate that MRP2 in the cell membrane may play an important role in regulating the cisplatin sensitivity of ESCC cells.
Cancer Science 02/2010; 101(6):1487-92. · 3.33 Impact Factor
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Akihiko Sano,
Shinji Sakurai,
Hiroyuki Kato,
Makoto Sakai,
Naritaka Tanaka,
Takanori Inose,
Kana Saito,
Makoto Sohda,
Masanobu Nakajima,
Kazuha Sakamoto,
Takaaki Sano,
Yoshinori Hosoya,
Takehiko Enomoto,
Tatsuo Kanda,
Yoichi Ajioka,
Tetsunari Oyama,
Hiroyuki Kuwano
[show abstract]
[hide abstract]
ABSTRACT: Esophageal carcinosarcoma is a very rare neoplasm and its clinicopathological characteristics and the prognostic factors that influence the clinical outcome of the patient remain a matter of controversy.
Twenty patients with esophageal carcinosarcoma were referred to our institutions. Tissue blocks were reviewed and sections containing both carcinomatous and sarcomatous components were stained for epithelial and mesenchymal markers and a proliferating cell marker. The prognosis of the esophageal carcinosarcoma patients was compared with 142 cases of esophageal squamous cell carcinoma.
In the carcinomatous component, the expression of cytokeratin, epithelial membrane antigen, vimentin, smooth muscle actin, and S100 were detected in 20, 20, 1, 1, and 1 case, respectively, whereas in the sarcomatous component, expression of these were detected in 4, 2, 18, 15, and 3 cases, respectively. The Ki-67 labeling index of carcinomatous and sarcomatous components was 35.5% and 41.8%, respectively. The 5-year survival rate was not statistically different between squamous cell carcinoma and carcinosarcoma (p=0.219). However, for T1 cases only, carcinosarcoma patients had statistically poorer prognosis than did squamous cell carcinoma patients (p=0.008).
The sarcomatous component shows various histological and immunohistochemical forms. In comparison with squamous cell carcinoma patients, carcinosarcoma patients had poorer prognosis amongst the T1 cases. For the treatment of esophageal carcinosarcoma, it is important to monitor lymph nodes and be watchful for hematogenous metastasis, as in cases of esophageal squamous cell carcinoma.
Anticancer research 09/2009; 29(8):3375-80. · 1.73 Impact Factor
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ABSTRACT: Lysyl oxidase (LOX), an extracellular matrix-remodeling enzyme, has been reported to regulate tumor metastasis. We investigated the clinical significance of LOX expression in esophageal squamous cell carcinoma (ESCC).
We examined LOX expression in ESCC cell lines by real-time reverse-transcriptase polymerase chain reaction (RT-PCR) and Western blotting. We also examined LOX expression by real-time RT-PCR in 39 surgically resected ESCC and by immunohistochemistry in 122 surgically resected ESCC.
LOX messenger RNA (mRNA) was expressed at a high level in TTn (originating from an ESCC metastatic lesion); at a moderate level in TE-2 and TE-15; and at a low level in TE-1, TE-8, and TE-13. In Western blotting, all cell lines expressed the catalytically inactive 50-kDa LOX at approximately the same levels, but catalytically active 32-kDa LOX was overexpressed only in TTn. LOX mRNA levels in ESCC tissues were significantly higher than those observed in normal esophageal tissues (P < 0.001) and had no significant correlation with tumor-node-metastasis (TNM) factors. High LOX protein expression had a significant correlation with presence of lymph node metastasis (P = 0.009) and number of lymph node metastases (P = 0.047). Overall and cancer-specific survival rates of patients with ESCC with high LOX expression were significantly lower than those of patients with ESCC with low LOX expression (P = 0.024 and P = 0.012). Univariate and multivariate analyses revealed that high LOX protein expression was an independent prognostic factor for ESCC.
Our findings suggest that LOX can serve as a predictive marker of lymph node metastasis and prognosis in ESCC.
Annals of Surgical Oncology 07/2009; 16(9):2494-501. · 4.17 Impact Factor
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Takanori Inose,
Hiroyuki Kato,
Hitoshi Kimura,
Ahmad Faried,
Naritaka Tanaka,
Makoto Sakai, Akihiko Sano,
Makoto Sohda,
Masanobu Nakajima,
Yasuyuki Fukai,
Tatsuya Miyazaki,
Norihiro Masuda,
Minoru Fukuchi,
Hiroyuki Kuwano
[show abstract]
[hide abstract]
ABSTRACT: Failure of gap junction formation affects the development of various types of cancer. We aimed to clarify the clinicopathologic outcome and prognostic significance of connexin (Cx) 26 in human esophageal squamous cell carcinoma (ESCC).
Immunohistochemical staining for Cx26 was performed on surgical specimens obtained from 123 patients with ESCC.
There was no positive staining for Cx26-specific expression in normal esophageal squamous cells. Primary ESCC with Cx26-positive expression was detected in the cytoplasm of cancer cell nests in 60 cases. Cx26 expression was correlated with N (lymph node metastasis, P = 0.014) and the number of metastatic lymph nodes (P = 0.047). The 5-year survival rates of ESCC patients with Cx26-positive expression were significantly lower than those with Cx26-negative expression (positive, 39.7%; negative, 65.7%; P = 0.007). By multivariate analysis, tumor-node-metastasis (TNM) clinical classification (T, P < 0.001; N, P = 0.002; M, P = 0.046) and Cx26 (P = 0.024) were independent prognosis predictors of ESCC.
These results suggest that abnormal expression of Cx26 participates in the progress of ESCC.
Annals of Surgical Oncology 04/2009; 16(6):1704-10. · 4.17 Impact Factor
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Akihiko Sano,
Hiroyuki Kato,
Shinji Sakurai,
Makoto Sakai,
Naritaka Tanaka,
Takanori Inose,
Kana Saito,
Makoto Sohda,
Masanobu Nakajima,
Takashi Nakajima,
Hiroyuki Kuwano
[show abstract]
[hide abstract]
ABSTRACT: Esophageal cancer is one of the most difficult malignancies to cure, and identification of novel prognostic markers for patients with this disease is important. CD24 is a small highly glycosylated mucin-like protein. Several studies have shown that higher CD24 expression is significantly associated with shorter patient survival in various malignant tumors. However, the expression of CD24 and its clinicopathological significance in esophageal cancer remain largely unknown. Immunohistochemical analyses of CD24 and Ki-67 overexpression in 151 cases of esophageal squamous cell carcinoma were performed to examine the relationships of CD24 expression with clinicopathological parameters and patient survival. Five cell lines derived from esophageal cancer were subjected to Western blot analyses to evaluate CD24 expression. Immunohistochemically, CD24 expression was judged to be positive in 61 (40.4%) cases. CD24 expression was associated with lymph node metastasis (p = 0.005), pathologic stage (p = 0.018), number of nodal metastases (p = 0.003), lymphatic invasion (p = 0.002), venous invasion (p < 0.001), and Ki-67 labeling index (p < 0.001). The Pearson's correlation coefficient between the CD24 expression score and the Ki-67 labeling index was 0.404 (p < 0.001). CD24 expression was associated with disease-free survival (p < 0.001). A Cox multivariate regression analysis revealed that CD24 expression was an independent prognostic factor (p = 0.033). On Western blot analysis, CD24 was detected in all five cell lines. We conclude that overexpression of CD24, which was correlated with Ki-67 expression, is a novel independent prognostic marker for identifying patients with poor prognosis after curative resection of esophageal squamous cell carcinoma.
Annals of Surgical Oncology 01/2009; 16(2):506-14. · 4.17 Impact Factor
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Hiroyuki Kato,
Hitoshi Kimura,
Masanobu Nakajima,
Makoto Sakai, Akihiko Sano,
Naritaka Tanaka,
Takanori Inose,
Ahmad Faried,
Kana Saito,
Keisuke Ieta,
Makoto Sohda,
Yasuyuki Fukai,
Tatsuya Miyazaki,
Norihiro Masuda,
Minoru Fukuchi,
Hitoshi Ojima,
Katsuhiko Tsukada,
Noboru Oriuchi,
Keigo Endo,
Hiroyuki Kuwano
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ABSTRACT: The purpose of the present study was to assess the contribution of simultaneous functional/anatomical imaging using integrated 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT), compared with PET alone for the evaluation of initial lymph node staging in esophageal cancer. We studied 167 consecutive patients with thoracic esophageal squamous cell carcinoma (SCC) who had radical esophagectomy performed between January 1999 and April 2007. For individual nodal group evaluation, PET/CT showed 46.0% sensitivity (p<0.05 vs. PET), 99.4% specificity, 95.1% accuracy (p<0.05 vs. PET), 87.0% positive and 95.5% negative predictive values. PET showed 32.9% sensitivity, 98.9% specificity, 93.1% accuracy, 74.7% positive predictive value and 93.9% negative predictive value. Thus, the sensitivity and accuracy of PET/CT were significantly higher than those of PET. Comparisons between CT, PET and PET/CT in detecting lymph node metastasis by each region showed that PET/CT had a higher sensitivity in lower thoracic regions than PET and CT (p<0.05 vs. CT and PET). Lymph node staging (N0 vs. N1) was not significantly different, but staging per lymph nodal group was significantly better with PET/CT. Integrated PET/CT imaging with co-registration of anatomic and functional imaging data is useful in the initial lymph node staging of patients with operable esophageal cancer compared with PET alone.
Oncology Reports 10/2008; 20(4):857-62. · 1.84 Impact Factor
