Biomedical subjects

Tadakazu Shimoda

Publications and source records attributed to Tadakazu Shimoda.

At least 19 recordsLinked to original sources

PubMed2006

Utility of immunohistochemical analysis for cyclo-oxygenase 2 in the differential diagnosis of osteoblastoma and osteosarcoma.

AIMS: To study the immunoexpression of cyclo-oxygenase (COX) 2 in osteoblastomas (OBs) and osteosarcomas (OSs), and to assess the utility of immunohistochemical analysis for COX 2 in the differential diagnosis of the two tumour forms. METHODS: The immunohistochemical features of COX 2 were studied in 11 OBs and 30 OSs, including 26 high-grade OSs (16 osteoblastic, 7 chondroblastic, and 3 fibroblastic) and 4 low-grade OSs. RESULTS: Tumour cells from all 11 OBs unequivocally showed diffuse, intense and cytoplasmic immunoreactivity for COX 2. Strong cytoplasmic expression of COX 2 was observed in 5 of 26 (19%) high-grade OSs, all chondroblastic. In one osteoblastic-type OS, COX 2 was expressed in the chondroblastic component, but this tumour was considered to be COX 2 negative. No COX 2 expression was noted in atypical osteoblastic cells. Staining in the four low-grade OSs was negative. CONCLUSION: The results of immunohistochemical analysis of COX 2 suggest that in addition to the routine histopathological evaluation, COX 2 is a valuable diagnostic marker in the distinction between OB and OS.

Adolescent↗

PubMed2006

Cyclooxygenase-2 overexpression associated with a poor prognosis in chondrosarcomas.

Recent studies have shown increased levels of cyclooxygenase (COX)-2 in various human malignancies, including some bone and soft tissue tumors, but little is known about the presence of COX-2 in chondrosarcomas. We performed immunohistochemical staining for COX-2 in 74 chondrosarcomas and compared the staining results with the characteristics and outcome of the patients. Thirty-seven men and 37 women between the ages of 14 and 81 years (median, 50 years) participated in the study. The tumors were located in the axial skeleton in 47 cases and in the long bones in 27 cases. The largest diameters of the tumors ranged from 2.7 to 32 cm (median, 8.0 cm). The immunohistochemistry findings revealed the overexpression of COX-2 in 16 (22%) of the 74 patients. Thirteen (41%) of 32 grade 2 and 2 (67%) of 3 grade 3 chondrosarcomas showed overexpression for COX-2, whereas only 1 (3%) of 39 grade 1 chondrosarcomas showed overexpression. Overexpression of COX-2 was significantly associated with histologic grade (P < .001) and a decreased disease-specific survival (P < .001). These findings suggest that COX-2 overexpression in chondrosarcoma is a negative prognostic factor that may be strongly associated with histologic grade.

Adolescent↗

PubMed2006

Histopathological criteria for additional treatment after endoscopic mucosal resection for esophageal cancer: analysis of 464 surgically resected cases.

No previous reports on lymph-node metastasis (LNM) from superficial squamous cell carcinoma of the esophagus have proposed definite criteria for additional treatment after endoscopic mucosal resection (EMR). We investigated the association between histopathological factors and LNM in 464 consecutive patients with superficial squamous cell carcinoma of the esophagus who had undergone a radical esophagectomy with lymph-node dissection (14 'M1' lesions: intraepithelial tumors, 36 'M2' lesions: tumors invading the lamina propria, 50 'M3' lesions: tumors in contact with or invading the muscularis mucosa, 32 'SM1' lesions: tumors invading the most superficial 1/3 of the submucosa and 332 'SM2/3' lesions: tumors invading deeper than SM1 level). Histopathological factors including invasion depth, size, lymphatic invasion (LY), venous invasion, tumor differentiation, growth pattern, degree of nuclear atypia and histological grade were assessed for their association with LNM in 82 M3 or SM1 lesions to determine which patients need additional treatment after EMR. LNM was found in 0.0, 5.6, 18.0, 53.1 and 53.9% of the M1, M2, M3, SM1 and SM2/3 lesions, respectively. A univariate analysis showed that each of the following histopathological factors had a significant influence on LNM: invasion depth (M3 vs SM1), LY, venous invasion and histological grade. Invasion depth and LY were significantly associated with LNM in a multivariate analysis. Four out of 38 patients (10.3%) with M3 lesions without LY had LNM, whereas five out of 12 patients (41.7%) with M3 lesions and LY had LNM. Only patients with M1/2 lesions are good candidates for EMR. Invading the muscularis mucosa (M3) is a high-risk condition for LNM the same as submucosal invasion, but M3 lesions without LY can be followed up after EMR without any additional treatment.

Adult↗

PubMed2006

Hedgehog signal activation in gastric pit cell and in diffuse-type gastric cancer.

BACKGROUND & AIMS: Sonic hedgehog (SHH) and Indian hedgehog (IHH) have cell-specific actions in some organs. Only SHH has been shown to regulate parietal cell differentiation. This study examined whether SHH, 2 other ligands IHH and Desert hedgehog, and receptors or downstream targets are expressed in normal gastric epithelium or in intestinal and diffuse-type gastric cancers. The effects of a Hedgehog (Hh) inhibitor, cyclopamine, were assessed in primary gastric epithelium cultures and gastric cancer cell lines. METHODS: Reverse-transcription polymerase chain reaction and immunostaining compared expression and localization of Hh signaling molecules and phenotypic markers of pit, neck, and gland cells in situ and in cultured cells treated with cyclopamine. Bromodeoxyuridine staining assessed the effects of cyclopamine on proliferation. RESULTS: Hh signaling molecules were expressed differentially in pit, neck, and gland cells. IHH co-expressed with most downstream targets in the pit. IHH, SHH, Patched (PTCH), Smoothened (SMO), and downstream targets were expressed more frequently and highly in the diffuse as compared with intestinal type cancers. In diffuse cancers, IHH was expressed in cells with an epithelial phenotype and SHH in cells with a mesenchymal phenotype. Cyclopamine reduced the number of cells with a pit phenotype but not a gland phenotype in primary cultures. Cyclopamine had particularly potent effects of inhibiting the growth of cell lines that expressed high levels of SMO. CONCLUSIONS: Expression of IHH and downstream targets correlates with pit cells. IHH and SMO may be useful biomarkers of diffuse cancers that may show growth inhibition with Hh antagonists such as cyclopamine.

Animals↗

PubMed2006

Interobserver variability in histologic recognition, interpretation of KIT immunostaining, and determining MIB-1 labeling indices in gastrointestinal stromal tumors and other spindle cell tumors of the gastrointestinal tract.

The authors studied the concordance among seven pathologists for the histologic diagnosis, interpretation of KIT immunostaining, and determining MIB-1 labeling indices (LI) in 80 adult patients with primary spindle cell tumors, mainly of the gastrointestinal tract, mesentery, retroperitoneum, and pelvis, based on the review of tissue sections using an immunohistochemical panel of antibodies for KIT/CD117, CD34, desmin, smooth muscle actin (SMA), and S-100 protein. Tumors included 30 gastrointestinal stromal tumors (GISTs), 10 leiomyomas, 10 leiomyosarcomas, 10 schwannomas, 10 solitary fibrous tumors, and 10 desmoid-type fibromatoses. The overall concordance with the original diagnosis of each histologic type was 97.9%, the kappa value ranging from 0.95 to 1.00 (mean 0.97), indicating a perfect agreement. The overall interlaboratory concordance with the original interpretation of KIT immunostaining was 91.3%, the kappa value ranging from 0.77 to 0.90 (mean 0.86). The overall interlaboratory concordance with the original interpretation of KIT immunostaining was 91.9%, the kappa value ranging from 0.72 to 0.93 (mean 0.85). The overall concordance for determining MIB-1 LI was 90% with the original evaluation, and the overall kappa value ranged from 0.62 to 0.86 (mean 0.77). These results indicate that it is possible to reliably diagnose GIST and other spindle cell tumors of the gastrointestinal tract with the use of an immunohistochemical panel of antibodies for KIT, CD34, desmin, SMA, and S-100 protein. Although there is clearly unavoidable inter-observer and interlaboratory variability in the interpretation of KIT immunostained sections and interobserver variability in the determination of MIB-1 LI, the concordance between observes is very acceptable, and in most instances such variability can be eliminated by careful reviewing of the hematoxylin and eosin and immunostained sections.

Adult↗

PubMed2006

Carcinoid tumor arising in a duplication cyst of the duodenum.

Reported herein is a case of carcinoid tumor arising in a duplication cyst of the duodenum in a 34-year-old woman. Ultrasonography at a health check-up revealed a 10 cm cystic mass located in the retroperitoneum adjacent to the third portion of the duodenum. Macroscopically, it had a smooth surface without communication with other organs and was filled with brownish necrotic fluid. More than half of the inner wall was occupied by a white, irregular, and solid nodule, which protruded into the lumen. The nodule was diagnosed as a carcinoid tumor invasive to the deep muscular layer. The non-neoplastic cyst wall had bowel structures including mucosa, submucosa and double layers of smooth muscle, indicating that the lesion was a duodenal duplication cyst. Most of the mucosa was eroded by marked inflammation. The remaining mucosa consisted of various types of epithelium, the major type having the nature of primitive gastric mucosa. Of interest was the presence of hamartomatous components in the wall. Furthermore, the non-neoplastic mucosal lining cells around the carcinoid tumor expressed neuroendocrine antigens and had minimal proliferative activity, suggesting that part of the cyst wall provided a microenvironment for accelerated differentiation of epithelial cells to an endocrine phenotype and transformation to neoplasia.

Adult↗

PubMed2006

Usefulness of Ki-67 for predicting the metastatic potential of rectal carcinoids.

Rectal carcinoid <10 mm can be completely removed by endoscopic procedure. However, a few authors reported that small rectal carcinoids have the potential to metastasize. Therefore, histological parameters predicting their metastatic potential are necessary. The aim of the present study was to evaluate the usefulness of Ki-67 positive/negative area ratio (Ki-67 ratio) using computer-assisted image analysis. A total of 43 patients with rectal carcinoids were retrospectively investigated. Twenty-eight patients underwent endoscopic resection and 15 patients underwent surgery. Nine of the 43 patients presented with metastatic disease. The Ki-67 ratio of all specimens was measured. Finally, the Ki-67 ratio was compared with other macroscopic or microscopic parameters for predicting lymph node or distant metastatic disease. The mean Ki-67 ratio of the metastatic and non-metastatic group was 3.9 and 1.0%, respectively (P < 0.01). The Ki-67 ratio was effective because of its high sensitivity (88.9%) and specificity (82.4%). Ki-67 ratio was superior to other microscopic parameters such as variation in nuclear size and vessel permeation. Ki-67 ratio was as effective as the other macroscopic parameters of tumor size and central depression. Based on these results it is suggested that Ki-67 is a reliable microscopic marker to predict metastatic potential of rectal carcinoids.

Carcinoid Tumor↗

PubMed2005

Distribution of the deepest penetrating point of minute submucosal gastric cancer.

BACKGROUND: Accurate assessment of depth of invasion is critical in decision-making for additional surgery after endoscopic resection of early gastric cancer (EGC). Although this depth of invasion is determined at the deepest point of submucosal invasion (DPSI), there is no literature describing the distribution of deepest invasion point. OBJECTIVE: To describe the location of the DPSI, and to determine whether it is possible to predict this point by clinicopathological features before treatment. METHODS: One hundred and ninety-five lesions of EGC with minute submucosal invasion, which had been resected en bloc between 1991 and 2003, were reviewed. For each lesion, we recorded the location of the DPSI as being in one of three areas demarcated by three concentric equal distance rings. We also examined the correlation between the location of the deepest penetration and the clinicopathological characteristics. RESULTS: The DPSI was located most often (53%) in the central, less often (31%) in the middle and least often (16%) in the outermost area. There was no significant correlation between the distribution of the deepest point and any clinicopathological features. CONCLUSIONS: The DPSI was not always in the central area, and it was impossible to predict its location by clinicopathological features alone. To obtain an accurate measure of depth of tumor invasion, we must histologically assess the entire lesion by thin sections.

Adenocarcinoma↗

PubMed2005

Bizarre parosteal osteochondromatous proliferation with a t(1;17) translocation.

Bizarre parosteal osteochondromatous proliferation (BPOP) is a benign lesion that tends to recur repeatedly. Histologically, BPOP contains three components (cartilage, bone, and spindle cells) in differing amounts. The histological findings of BPOP are similar to those of florid reactive periostitis (FRP) and subungual (Dupuytren's) exostosis. Some authors have postulated that all of these conditions are reactive proliferative lesions representing different phases of reactive processes. Whether BPOP is a reactive proliferative lesion or a neoplastic lesion, however, remains controversial. Recently, a t(1;17)(q32;q21) translocation in BPOP was detected using chromosome banding and fluorescence in situ hybridization (FISH) analyses. Here, we describe a 39-year-old Japanese female with BPOP arising in the proximal phalanx of her third toe. A cytogenetic analysis revealed a t(1;17)(q 42;q23) translocation. The breakpoints in this case are located close to those of previously reported cases. These results suggest that t(1;17) is a distinct translocation of BPOP and that BPOP is a neoplastic lesion, rather than a reactive proliferative process.

Adult↗

PubMed2005

Predictive histopathologic factors for lymph node metastasis in patients with nonpedunculated submucosal invasive colorectal carcinoma.

PURPOSE: Risk factors for lymph node metastasis in patients with nonpedunculated submucosal invasive colorectal carcinoma remain to be characterized. This study examines the relationship between lymph node metastasis and clinicopathologic factors in nonpedunculated submucosal invasive colorectal carcinoma. METHODS: The study cohort comprised 155 patients who had undergone surgical treatment for nonpedunculated submucosal invasive colorectal carcinoma. The clinicopathologic factors investigated included gender, age, tumor location, macroscopic type, tumor size, histologic type and grade, intramucosal growth pattern, lymphatic invasion, venous invasion, degree of focal dedifferentiation at the submucosal invasive front, status of the remaining muscularis mucosa, and the depth and width of submucosal invasion. RESULTS: Lymph node metastases were found in 19 patients (12.3 percent). Univariate analysis showed that lymphatic invasion, focal dedifferentiation at the submucosal invasive front, status of the remaining muscularis mucosa, and depth of submucosal invasion all had a significant influence on lymph node metastasis. Multivariate analysis showed lymphatic invasion (P = 0.014) and high-grade focal dedifferentiation at the submucosal invasive front (P = 0.049) to be independent factors predicting lymph node metastasis. No lymph node metastasis was found in tumors with a depth of submucosal invasion of <1.3 mm. CONCLUSIONS: Lymphatic invasion and high-grade focal dedifferentiation at the submucosal invasive front are important predictors of lymph node metastasis in patients with nonpedunculated submucosal invasive colorectal carcinoma. Depth of submucosal invasion can be used as an identifying marker for patients who do not require subsequent surgery after endoscopic resection.

Aged↗

PubMed2005

CD10 expression in colorectal carcinoma correlates with liver metastasis.

PURPOSE: If it were possible to identify the features of primary colorectal carcinoma that were associated with liver metastasis, these features could be used as predictors of liver metastasis. METHODS: From January 1995 to December 1997, 648 consecutive cases of colorectal carcinoma were recorded at the Department of Surgery, National Cancer Center Hospital, Tokyo, Japan. We evaluated clinicopathologic and immunohistochemical factors (age, gender, tumor location, gross type, size, histologic type, dedifferentiation of invasive front, depth of invasion, lymphatic invasion, venous invasion, lymph-node metastasis, and expression of CD10, MUC2, and human gastric mucin) in 505 of these patients who had undergone resection of T2/T3/T4 colorectal carcinomas to clarify the correlation between these factors and liver metastasis. RESULTS: Liver metastases, including unresectable, were detected in 122 patients (24 percent), all of whom had been followed for at least five years. Univariate analysis revealed that liver metastasis was significantly associated with tumor size, histologic type, dedifferentiation of invasive front, depth of invasion, lymphatic invasion, venous invasion, lymph-node metastasis, and CD10 expression. Multivariate analysis revealed that invasion deeper than the subserosa, venous invasion, lymph-node metastasis, and CD10 expression were significantly associated with liver metastases. CONCLUSIONS: CD10 expression in colorectal carcinoma is a good predictor of liver metastasis.

Adenocarcinoma↗

PubMed2004

Frequent hypermethylation of RASSF1A in early flat-type colorectal tumors.

Flat colorectal tumors, characterized by high-grade dysplasia from early small flat mucosal lesions, exhibit a relatively aggressive clinical behavior and are known for their infrequent K-ras mutations. In this study, we investigated the methylation status of the RASSF1A promoter in association with 3p LOH and K-ras mutations in 48 flat colorectal tumors (39 early carcinomas and nine intramucosal high-grade dysplasias). RASSF1A hypermethylation was detected in 39 of 48 (81.3%) tumors and RASSF1A methylation was also detected in 19 of 39 (49%) normal colonic mucosal tissues. 3p21.3 LOH was detected in 20 of 42 (47.6%) cases, but RASSF1 methylation was detected in cases with LOH (14 cases) and retention of 3p21.3 (20 cases). K-ras mutations were detected in seven of 48 (14.6%) tumors and the concordant occurrence of K-ras mutation and RASSF1A methylation was detected in three of 48 cases (6.3%). Overall, there was a statistically significant mutually exclusive relationship between K-ras mutations and RASSF1A methylation. In conclusion, promoter hypermethylation of RASSF1A is a frequent event and may start early in the background normal mucosa in this tumor type. An alternative cascade of abnormalities in RAS transduction pathways may be responsible for the flat morphology and aggressive nature of flat colorectal neoplasms.

Adult↗

PubMed2004

Differential diagnosis of gastrointestinal stromal tumor and other spindle cell tumors in the gastrointestinal tract based on immunohistochemical analysis.

To confirm the usefulness of an immunohistochemical panel of antibodies for KIT (c-kit/CD117), CD34, desmin, smooth-muscle actin (SMA), h-caldesmon (HCD), S-100 protein, neuron-specific enolase (NSE), and beta-catenin, 297 mesenchymal and peripheral nerve-sheath tumors of the gastrointestinal tract and intra-abdominal locations including 211 gastrointestinal stromal tumors (GISTs), 12 leiomyomas, 18 leiomyosarcomas, 17 solitary fibrous tumors (SFTs), 14 schwannomas, and 25 desmoid-type fibromatoses (DTFs) were analyzed immunohistochemically. Consistent (100%) immunoreactivity for KIT, CD34, desmin and S-100, and nuclear accumulation of beta-catenin were detected in GISTs, SFTs, smooth-muscle tumors, schwannomas, and DTFs, respectively. Immunoreactivity for SMA, HCD, and NSE was observed in a wide range of these tumors. In addition, 418 bone and soft tissue tumors were enrolled in this study for KIT immunostaining. As a result, a limited number of these tumors were KIT positive, including synovial sarcoma that showed morphological similarity to GISTs. These findings suggest that KIT, CD34, desmin, S-100, and beta-catenin are key markers for clinical diagnosis of GISTs and other spindle cell tumors that may involve the gastrointestinal tract, whereas SMA, HCD, and NSE have only limited value.

Antigens, CD34↗

PubMed2004

Correlations between lymph node metastasis and depth of submucosal invasion in submucosal invasive colorectal carcinoma: a Japanese collaborative study.

BACKGROUND: Depth of submucosal invasion (SM depth) in submucosal invasive colorectal carcinoma (SICC) is considered an important predictive factor for lymph node metastasis. However, no nationwide reports have clarified the relationship between SM depth and rate of lymph node metastasis. Our aim was to investigate the correlations between lymph node metastasis and SM depth in SICC. METHODS: SM depth was measured for 865 SICCs that were surgically resected at six institutions throughout Japan. For pedunculated SICC, the level 2 line according to Haggitt's classification was used as baseline and the SM depth was measured from this baseline to the deepest portion in the submucosa. When the deepest portion of invasion was limited to above the baseline, the case was defined as a head invasion. For nonpedunculated SICC, when the muscularis mucosae could be identified, the muscularis mucosae was used as baseline and the vertical distance from this line to the deepest portion of invasion represented SM depth. When the muscularis mucosae could not be identified due to carcinomatous invasion, the superficial aspect of the SICC was used as baseline, and the vertical distance from this line to the deepest portion was determined. RESULTS: For pedunculated SICC, rate of lymph node metastasis was 0% in head invasion cases and stalk invasion cases with SM depth <3000 micro m if lymphatic invasion was negative. For nonpedunculated SICC, rate of lymph node metastasis was also 0% if SM depth was <1000 micro m. CONCLUSIONS: These results clarified rates of lymph node metastasis in SICC according to SM depth, and may contribute to defining therapeutic strategies for SICC.

Adult↗

PubMed2004

Myxoid epithelioid gastrointestinal stromal tumor (GIST) with mast cell infiltrations: a subtype of GIST with mutations of platelet-derived growth factor receptor alpha gene.

We analyzed 30 gastrointestinal stromal tumors (GISTs) that were immunohistochemically weak or negative for KIT. Histologically, all 30 GISTs consisted of epithelioid tumor cells in at least a part of the tumor. The tumor cells showed different morphologies and arranged themselves in different histological patterns. In 20 of the 30 GISTs, round or oval epithelioid tumor cells often showed a less cohesive pattern of growth and showed eosinophilic cytoplasm and peripherally placed nuclei with myxoid stroma, whereas in the remaining 10 cases, tumor cells were arranged in a more cohesive pattern without myxoid stroma. The former type of tumors is called myxoid epithelioid GISTs in this study. Subsequent mutational analyses showed that the platelet-derived growth factor receptor alpha (PDGFRA) gene mutations in exon 12 or exon 18 were identified in 20 (66.7%) of the 30 GISTs, and especially in 18 (90%) of the 20 myxoid epithelioid GISTs. Moreover, 17 (85%) of the 20 myxoid epithelioid GISTs were accompanied by mast cell infiltrations within the tumor nodules. In the remaining cases, 2 (6.7%) of the 30 GISTs had c-kit gene mutations in exon 11, and no mutation was found in 8 (26.7%) of 30 GISTs. None of the patients with myxoid epithelioid GISTs died of disease. These results suggest that myxoid epithelioid GISTs are a distinct subtype of GISTs that are closely correlated with the PDGFRA gene mutation and that recognition of such histological characteristics should be helpful for molecular subclassification of GISTs that are important for molecular targeting therapy by imatinib mesylate (STI571).

Adult↗

PubMed2004

High-grade dysplasia associated with fundic gland polyposis in a familial adenomatous polyposis patient, with special reference to APC mutation profiles.

We report a patient with familial adenomatous polyposis who developed high-grade dysplasia against a background of fundic gland polyposis. Two large high-grade dysplasia lesions were found in the gastric body, where numerous fundic gland polyps were present. In both lesions, the dysplastic epithelium covered non-neoplastic oxyntic glands that occasionally exhibit cystic changes. A genetic analysis for APC (adenomatous polyposis coli) revealed a somatic 50-bp deletion involving codons 1502-1517 and 2-bp deletion at codon 1465 in each lesion of high-grade dysplasia. In contrast, six of the 18 fundic gland polyps were found to harbor an identical mutation: 1-bp insertion at codon 1556. Both lesions of high-grade dysplasia and the fundic gland polyps were similarly located in the fundic gland area and were caused by the inactivation of APC; however, their mutation profiles of APC were different. These results imply that fundic gland polyps and high-grade dysplasia of the stomach have distinct preferences for APC genotypes in their development.

Adenomatous Polyposis Coli↗

PubMed2004

Adenosquamous carcinoma of the esophagus. Clinicopathologic study of 18 cases.

OBJECTIVES: Adenosquamous carcinoma (ASC) of the esophagus is an uncommon form of esophageal cancer. Despite isolated case reports on this tumor type, no large clinicopathologic series appears to have been studied at a single institution. METHODS: At our institution, 20 cases of ASC were diagnosed pathologically between 1970 and 2001 (20/2,056 total esophageal cancers; 1.0%). Excluding 2 patients who received preoperative radiation therapy, 18 were selected for review of their clinicopathologic features, including survival time, in comparison with those of patients with conventional squamous cell carcinomas (SCCs; n = 850) and adenocarcinomas (ACs; n = 40) of the esophagus. RESULTS: The location and macroscopic type of the ASCs were similar to those of the SCCs. ASC tumors were significantly smaller than SCC (p = 0.004) and AC (p = 0.012) tumors, and the depth of invasion of ASCs was significantly less than that of SCCs (p = 0.028). Lymphatic permeation and blood vessel invasion were seen in 14 (77.8%) and 7 (38.9%) of the 18 patients with ASCs, respectively, and intraepithelial carcinoma contiguous to the main lesion was evident in 10 cases (56.6%). The cumulative postoperative survival rates of patients with ASC at 3, 5 and 10 years were 71.5, 63.6 and 47.7%, respectively, the outcome being significantly better than for patients with either SCC (p = 0.027) or AC (p = 0.013). CONCLUSION: In the esophagus, ASCs have better prognosis than conventional SCCs or ACs, probably due to their smaller size and lower stage.

Aged↗

PubMed2003

Association of gastric and intestinal phenotypic marker expression of gastric carcinomas with tumor thymidylate synthase expression and response to postoperative chemotherapy with 5-fluorouracil.

PURPOSE: It is well known that both gastric and intestinal phenotypic markers are expressed in gastric carcinomas, irrespective of their histological type. In the present study, the associations among phenotypic marker expression of gastric carcinomas, tumor thymidylate synthase (TS) expression, and the chemotherapeutic response to 5-fluorouracil (5-FU) were examined. METHODS: The gastric and intestinal phenotypic marker expression of the tumor was determined by the combination of the expression of human gastric mucin (HGM), MUC6, MUC2, and CD10, and was evaluated in comparison with tumor TS expression in 137 advanced gastric carcinomas in 137 patients (75 with postoperative chemotherapy with 5-FU and 62 without postoperative chemotherapy). Tumors were classified into the gastric- (G-), gastric and intestinal mixed- (GI-), intestinal- (I-), or unclassified- (UC-) phenotype according to the immunopositivity of HGM, MUC6, MUC2, and CD10 stainings. The associations among the gastric and intestinal phenotypic marker expression of the tumor, tumor TS expression, effect of postoperative chemotherapy with 5-FU, and the patient's prognosis were examined. RESULTS: Of the 137 gastric carcinomas, 48 (35.0%), 58 (42.3%), 23 (16.8%), and 8 (5.8%)were classified as the G-, GI-, I- and UC-phenotype, respectively. The high TS expression of more than 25% tumor cell positivity was found in 25 (52.1%) of the 48 G-phenotype tumors, 39 (67.2%) of the 58 GI-phenotype tumors, 18 (78.3%) of the 23 I-phenotype tumors, and 4 (50.0%) of the 8 UC-phenotype tumors. The I-phenotype tumors were significantly correlated with the higher rate of the high TS expression as compared with the G-phenotype tumors (P<0.05). Among 48 patients with the G-phenotype tumor, the 5-year survival rate in patients with and without postoperative chemotherapy was 39.7 and 27.8%, respectively. The patients with postoperative chemotherapy had a significantly better prognosis than those without postoperative chemotherapy (P<0.05). Conversely, there were no significant correlations between the presence of postoperative chemotherapy and the patient's prognosis among patients with GI-, I-, and UC-phenotype tumors. CONCLUSIONS: These results indicate that postoperative chemotherapy with 5-FU could be effective for patients with the G-phenotype tumor, since the incidence of intratumoral expression of TS, the target enzyme of 5-FU, is significantly low in G-phenotype tumors.

Aged↗