High levels of DNA polymerase ß mRNA corresponding with the high activity in Graves' thyroid tissue.

INTRODUCTION: High DNA polymerase ß activity has been observed in the thyroid tissue of patients with Graves' disease (Nagasaka et al. in Metabolism 37:1051-1054, 1988). This fact aroused our interest in whether the alteration of DNA polymerase ß activity depends on DNA polymerase ß (DNA poly ß) mRNA levels, which may be modulated by thyroid-stimulating hormone (TSH) or thyroid-stimulating substances, i.e. TSH receptor antibody (TRAb). RESULT: Addition of TSH or TRAb to primary cultures of Graves' disease thyroid cells for 4 h led to no increase in DNA poly ß mRNA levels. In contrast, thyroid hormone synthesizing enzyme, peroxidase, mRNA levels increased fivefold after coculture with TSH and TRAb, even though DNA poly ß activity and mRNA levels are already significantly higher in Graves' disease thyroid tissues, compared with normal thyroid tissue. DISCUSSION: These results indicate that DNA poly ß expression in Graves' disease thyroid cells may be maximally activated or plateau in response to thyroid-stimulating immunoglobulins, or that the activation of to poly ß expression may occur via pathways other than the G protein and cyclic AMP system.

Prognostic value of histological type in stage IV ovarian carcinoma: a retrospective analysis of 223 patients.

BACKGROUND: Patients with FIGO stage IV epithelial ovarian carcinoma have a poor but non-uniform prognosis. This study aimed to compare the survival of patients with serous or endometrioid tumours (S/E) and clear cell or mucinous tumours (non-S/E). METHODS: Data for 223 patients who underwent surgery between 1987 and 2010 and were diagnosed by centralized pathology review and were retrospectively analysed. The patients included 169 with S/E tumours and 54 with non-S/E tumours. RESULTS: The median overall survivals (OSs) of the S/E and non-S/E groups were 3.1 and 0.9 years, respectively (P<0.001). Six patients (2.7%), all with non-S/E tumours, died within 6 weeks after the initial surgery. Multivariate OS analysis revealed that performance status, residual tumor, metastatic sites, no debulking surgery, and non-S/E tumours were independent poor prognostic factors. For patients with non-S/E tumours, prognosis was more favourable for single-organ metastasis, except for liver or distant lymph nodes, no residual tumor, and resection of metastasis (median OS: 4.1, 4.6, and 2.6 years, respectively). CONCLUSIONS: In stage IV ovarian carcinoma, non-S/E tumours are associated with a significantly poorer prognosis and higher rates of early mortality compared to S/E tumours. Therefore, careful management and development of new strategies are required.

Five-year clinical results for treatment of intrabony defects with EMD, guided tissue regeneration and open-flap debridement: a case series.

BACKGROUND AND OBJECTIVE: Although regenerative periodontal surgery with EMD or guided tissue regeneration (GTR) has been shown to enhance periodontal regeneration, there are limited data on the long-term results following these treatment modalities. The purpose of the present study was to investigate the long-term clinical outcomes in intrabony defects following regenerative periodontal surgery with EMD or GTR compared with open-flap debridement (OFD). MATERIAL AND METHODS: Data from 40 subjects (44 teeth), with no history of smoking or systemic diseases that could interfere with periodontal disease and who received one of three surgical procedures (EMD, GTR or OFD) for two- or three-wall intrabony defects, were analyzed. Postoperative reduction in probing pocket depth, gain in clinical attachment level, gingival recession and percentage bone fill were compared at 1, 3 and 5 years. RESULTS: Reduction in probing pocket depth after GTR was significantly higher than after OFD at 1 and 3 years postoperatively, but there was no difference between the groups at 5 years. The gains in clinical attachment level for EMD (at 3 and 5 years) and for GTR (at 1, 3 and 5 years) were significantly greater than for OFD. Gingival recession after treatment with EMD and GTR showed a tendency toward positive results, whereas no such tendency was observed for OFD. Postoperative percentage bone fill for EMD and GTR was significantly greater than for OFD at 3 and 5 years. CONCLUSIONS: This is a retrospective study and an exploratory report with a high risk of bias. Within the limits of the current study, it may be concluded that superior gains in clinical attachment level and improved percentage bone fill can be obtained with EMD and GTR when compared with OFD, and these can be maintained over a period of 5 years.

Differential Expression of Claudin 1 and 4 in Basal Cell Carcinoma of the Skin.

Basal cell carcinoma (BCC) is the most common human malignancy. The biological behavior of this entity is remarkably indolent. Claudin plays an important role in tight junctions, regulating paracellular passage of variable substance including growth factors and maintaining the polarity of epithelia. Up- or downregulated claudin expression has been reported in many cancers. Nevertheless, claudin expression in BCC of the skin remains unclear. We therefore examined the status of claudin 1 and 4 expressions in BCC and adjacent normal skin by immunohistochemistry (IHC). Our IHC results demonstrated high claudin 1 expression and low claudin 4 expression in 33 of 34 lower-grade BCCs. In lower-grade BCC, claudin 1 was increased and claudin 4 was decreased compared with the normal skin. Claudin 1 was inclined to be highly expressed in the membrane and cytoplasm of tumour cells in the periphery of tumour nest. Conversely, almost all lower-grade BCCs (33/34) and one of two higher-grade BCC lacked or showed focal positivity for claudin 4. These results imply that the expression pattern is characteristics of lower-risk BCC. Interestingly, one of the two higher-grade BCCs demonstrated the converse expression patterns of claudins, with decreased claudin 1 and increased claudin 4. The combination of immunohistochemical claudin 1 and 4 expression may offer a useful ancillary tool for the pathological diagnosis of BCC. Furthermore, membranous and intracellular claudins may present future therapeutic targets for uncontrollable BCC.

CT findings of intraductal papillary neoplasm of the bile duct: assessment with multiphase contrast-enhanced examination using multi-detector CT.

AIM: To evaluate multi-detector computed tomography (MDCT) findings of intraductal papillary neoplasm of the bile duct (IPNB), a neoplasm that is considered to be the biliary counterpart of pancreatic intraductal papillary mucinous neoplasm. MATERIALS AND METHODS: Two radiologists retrospectively evaluated multiphase contrast-enhanced CT images with 0.5 or 1mm collimation in 37 consecutive patients with resected IPNB diagnosed by a single pathologist. The CT findings were correlated with the pathological findings concerning invasion of the surrounding organs and vessels. RESULTS: All patients showed bile duct dilatation. An intraductal mass was detected in 36 patients and the following findings were observed: extensive infiltration along the bile duct more than 20mm (n=32), compared with normal hepatic parenchyma, isodense or hyperdense during the late arterial phase (n=31), not hyperdense during the portal-venous and delayed phases (n=36), and intense enhancement rim at the base of the mass during the portal-venous or delayed phase (n=27). Parenchymal invasion of the surrounding organs was seen in eight of 16 tumours showing irregular or bulging margins. Vascular invasion was false positive in four of eight tumours. CONCLUSIONS: IPNB exhibits relatively characteristic findings with multiphase contrast-enhanced examination using MDCT. A tendency to overestimate invasion of the surrounding organs and vessels was seen.

Long-term survival of young women receiving fertility-sparing surgery for ovarian cancer in comparison with those undergoing radical surgery.

OBJECTIVES: To compare the clinical outcome of patients with stage I epithelial ovarian cancer (EOC) who received with fertility-sparing surgery (FSS) with those who underwent radical surgery (RS). METHODS: After a central pathological review and search of the medical records from multiple institutions, a total of 572 patients were retrospectively evaluated. All patients were divided into three groups: group A {FSS (n=74); age, ≤ 40}; groups B and C [RS; age, 40 ≥{(B), n=52}; 40<{(C), n=446}]. RESULTS: Five-year overall survival (OS) and disease-free survival (DFS) rates of patients in the groups were as follows: group A, 90.8% (OS)/87.9% (DFS); group B, 88.3% (OS)/84.4% (DFS); group C, 90.6% (OS)/85.3% (DFS), respectively (OS, P=0.802; DFS, P=0.765). Additionally, there was no significant difference in OS and DFS among the three groups stratified to stage IA or IC (OS (IA), P=0.387; DFS (IA), P=0.314; OS (IC), P=0.993; DFS (IC), P=0.990, respectively). Furthermore, patients with a grade 1-2 or 3 tumours in the FSS group did not have a poorer prognosis than those in the RS group. CONCLUSIONS: Stage I EOC patients treated with FSS showed an acceptable prognosis compared with those who underwent RS.

BDCA-2, a novel plasmacytoid dendritic cell-specific type II C-type lectin, mediates antigen capture and is a potent inhibitor of interferon alpha/beta induction.

Plasmacytoid dendritic cells are present in lymphoid and nonlymphoid tissue and contribute substantially to both innate and adaptive immunity. Recently, we have described several monoclonal antibodies that recognize a plasmacytoid dendritic cell-specific antigen, which we have termed BDCA-2. Molecular cloning of BDCA-2 revealed that BDCA-2 is a novel type II C-type lectin, which shows 50.7% sequence identity at the amino acid level to its putative murine ortholog, the murine dendritic cell-associated C-type lectin 2. Anti-BDCA-2 monoclonal antibodies are rapidly internalized and efficiently presented to T cells, indicating that BDCA-2 could play a role in ligand internalization and presentation. Furthermore, ligation of BDCA-2 potently suppresses induction of interferon alpha/beta production in plasmacytoid dendritic cells, presumably by a mechanism dependent on calcium mobilization and protein-tyrosine phosphorylation by src-family protein-tyrosine kinases. Inasmuch as production of interferon alpha/beta by plasmacytoid dendritic cells is considered to be a major pathophysiological factor in systemic lupus erythematosus, triggering of BDCA-2 should be evaluated as therapeutic strategy for blocking production of interferon alpha/beta in systemic lupus erythematosus patients.

CT findings in autoimmune pancreatitis: assessment using multiphase contrast-enhanced multisection CT.

AIM: To assess the spectrum of findings using multiphase contrast-enhanced computed tomography (CT) in patients with autoimmune pancreatitis (AIP). MATERIALS AND METHODS: Fifty patients (four female and 46 male, mean age 65 years) were retrospectively identified from consecutive patients with abnormal CT findings of the pancreas and negative work-up for known causes. These patients had at least one finding supporting the diagnosis of AIP: serological abnormality, histopathological abnormality, or response to steroid. Two radiologists evaluated multiphase contrast-enhanced CT images in consensus. RESULTS: The pancreas showed diffuse enlargement (n=16; 32%), focal enlargement (n=18; 36%), or no enlargement (n=16; 32%). Forty-nine (98%) patients showed abnormal contrast enhancement in the affected pancreatic parenchyma, including hypoattenuation during the pancreatic phase (n=45; 90%) and hyperattenuation during the delayed phase (n=39; 87%). The following findings were also seen in the pancreas: a capsule-like rim (n=24; 48%); no visualization of the main pancreatic duct lumen (n=48; 96%); ductal enhancement (n=26; 52%); upstream dilatation of the main pancreatic duct (n=27; 54%); upstream atrophy of the pancreatic parenchyma (n=27; 54%); calcification (n=7; 14%); and cysts (n=5; 10%). Forty-two (84%) patients showed one or more of the following extrapancreatic findings: biliary duct or gallbladder abnormality (n=40; 80%); peripancreatic (n=8; 16%) or para-aortic (n=10; 20%) soft-tissue proliferation; and renal involvement (n=15; 30%). CONCLUSION: Patients with AIP presented with a variety of CT findings in the pancreas and the extrapancreatic organs. The present study highlights pancreatic ductal enhancement in a subset of patients with AIP.

The concept of perihilar cholangiocarcinoma is valid.

BACKGROUND: The term perihilar cholangiocarcinoma has been used for all tumours involving or requiring resection of the hepatic confluence. However, it does not distinguish between intrahepatic and extrahepatic hilar tumours, and has no clinicopathological basis. This retrospective study examined whether the concept of perihilar cholangiocarcinoma is valid clinically. METHODS: Some 250 patients with perihilar cholangiocarcinoma were divided into extrahepatic (EHC, 167 patients) and intrahepatic (IHC, 83) groups based on tumour location. Clinicopathological data were compared between these groups. RESULTS: Liver, portal vein, venous and lymphatic invasion, and nodal metastasis were more common in IHCs than EHCs, whereas histological grade and incidence of perineural invasion were similar. IHCs were more advanced at the time of surgery; stage III or IV disease was found in 37.7 per cent of EHCs and 59 per cent of IHCs. Survival was marginally better for patients with EHCs than for those with IHCs (29.3 versus 20 per cent at 5 years; P = 0.057), but survival rates were similar for each tumour stage in the American Joint Committee on Cancer classification. CONCLUSION: Combining EHC and IHC under the term perihilar cholangiocarcinoma is valid, as these tumours have comparable biological behaviour, with similar clinical management depending on stage and invasion.

Lymphoplasmacytic sclerosing cholangitis: assessment of clinical, CT, and pathological findings.

AIM: To assess the clinical, computed tomography (CT), and pathological findings in patients with lymphoplasmacytic sclerosing cholangitis. MATERIALS AND METHODS: Fifteen consecutive patients (four women and 11 men, mean age 71 years) with lymphoplasmacytic sclerosing cholangitis and without the characteristic features of underlying disorders causing benign biliary strictures were retrospectively recruited. Two radiologists evaluated multiphase contrast-enhanced CT images acquired with 0.5 or 1-mm collimation. One pathologist performed all histological examinations, including IgG4 immunostaining. RESULTS: The intrahepatic biliary ducts showed dilatation in all 15 patients, but only seven presented with jaundice. Although laboratory data were not available in all patients, serum gammaglobulin and IgG levels were elevated in five of six patients and six of eight patients, respectively. Anti-nuclear antibody was detected in three of six patients. The involved biliary ducts showed the following CT findings: involvement of the hilar biliary duct (14/15), a mean wall thickness of 4.9 mm, a smooth margin (10/15), a narrow but visible lumen (6/15), hyper-attenuation during the late arterial phase (9/15), homogeneous hyper-attenuation during the delayed phase (11/11), and no vascular invasion (14/15). Abnormal findings in the pancreas and urinary tract were detected in eight of 15 patients. In 13 patients with adequate specimens, moderate to severe lymphoplasmacytic infiltration associated with dense fibrosis was observed. Infiltration of IgG4-positive plasma cells was moderate or severe in nine patients and minimal or absent in four patients. CONCLUSION: Lymphoplasmacytic sclerosing cholangitis exhibits relatively characteristic clinical and CT findings, although they are not sufficiently specific for differentiation from other biliary diseases.

Methylation in p14(ARF) is frequently observed in colorectal cancer with low-level microsatellite instability.

Colorectal cancer (CRC) can be classified as high-level microsatellite instability (MSI-H), low-level MSI (MSI-L) and microsatellite stable (MSS) depending on levels of MSI. MSI-H CRC relies on a distinct molecular pathway due to the mismatch repair (MMR) deficiency and shows methylation in multiple gene promoters. The genetic pathway leading to MSI-L is unknown, although higher levels of promoter methylation are observed in this group compared with MSS CRCs. This study explored how promoter methylation affects MSI phenotype, by analysing the methylation status of eight CRC-related promoters, MSI phenotype and KRAS/BRAF mutations in a series of 234 CRCs. Promoter methylation of p14(ARF) was significantly related to MSI-L CRC with KRAS mutation. The MSI-H phenotype was related to methylation of MLH1 as expected, while the MSS phenotype was related to methylation of p16(INK4a) and O(6)-methylguanine-DNA methyltransferase, although this was not statistically significant. Thus, promoter methylation of p14(ARF) could be a significant alteration leading to CRC with MSI-L.

Is there any association between retroperitoneal lymphadenectomy and survival benefit in ovarian clear cell carcinoma patients?

BACKGROUND: To estimate the survival impact of systemic retroperitoneal lymphadenectomy in patients diagnosed with International Federation of Gynecology and Obstetrics pTI-IIb clear cell carcinoma of the ovary (CCC). PATIENTS AND METHODS: Demographic and clinicopathologic data were obtained from the Tokai Ovarian Tumor Study Group between 1986 and 2006. Survival curves were calculated using the Kaplan-Meier method. Differences in survival rates were analyzed using the log-rank test. RESULTS: A total of 205 patients had clinical pTI-IIb CCC (median age: 52 years, range: 30-75). One hundred and four (50.7%) patients underwent systemic retroperitoneal lymphadenectomy. Lymphadenectomy was not associated with improved disease-free and overall survival in all patients (P = 0.353 and P = 0.645, respectively). Moreover, lymphadenectomy did not improve the overall survival in those with pTIc CCC (P = 0.433). Similarly, on univariate analysis, age, volume of ascites, preoperative CA 125 values, and regimen of chemotherapy were not significant factors. In addition, there was no significant difference in the ratio of positive lymph node metastases regardless of the completion of lymphadenectomy (P = 0.955). CONCLUSION: Our data suggest that patients with pTI-IIb CCC who underwent lymphadenectomy did not show a significant improvement in survival. There was no significant difference in the overall and disease-free survival rates in pTI-IIb CCC patients regardless of the completion of surgical staging lymphadenectomy.

Persistent lymphoedema in Morbihan disease: formation of perilymphatic epithelioid cell granulomas as a possible pathogenesis.

Morbihan disease is a rare complication of rosacea, characterized by persistent lymphoedema on the upper half of the face, occurring during the chronic clinical course of rosacea. This refractory condition has been also designated as 'rosacea lymphoedema' and 'solid persistent facial oedema of rosacea'. We report a patient with Morbihan disease showing persistent lymphoedema on the upper half of the face accompanied by unique histological findings of striking dermal dilated lymphatics and damage of the lymphatics at the site of the adjacent epithelioid cell granulomas, with histiocytes bulging into the lymphatic lumen. The marked epithelioid cell granulomas forming around dermal lymphatic vessels with subsequent lymphatic damage and luminal obstruction by histiocytic infiltration may account for the development of lymphoedema in this patient.

Inflation-deflation method for endoscopic evacuation of intracerebral haematoma.

BACKGROUND: Endoscopic evacuation of intracerebral haematoma (ICH) has the advantage of being less invasive than craniotomy, but limited visualisation and difficulties in haemostasis are still a concern. The collapse of the haematoma cavity limits the visualisation of the surgical field. Inflation of the haematoma cavity with saline irrigation improves visualisation and facilitates accurate intra-operative orientation. METHOD: A unique technique, the cavity inflation-deflation method can help in exploring the residual haematoma and accessing the bleeding points. We also developed a combined irrigation-coagulation suction tube that concentrates the capabilities of suction, irrigation and monopolar coagulation. FINDINGS: The use of this multifunctional dedicated instrument and its application in the cavity inflation-deflation method allows for easy identification of residual haematoma and bleeding vessels. Secure haemostasis can also be accomplished under clear visualisation. No surgical complications and rebleeding occurred in any patient following the procedure. Our results show that the median haematoma evacuation rate was 99% and the surgical outcome was satisfactory. CONCLUSIONS: The inflation-deflation method using a combined irrigation-coagulation suction tube can facilitate optimal evacuation of ICH with secure haemostasis. Although further accumulation of patients and careful analyses are needed to be known whether this procedure improves the clinical outcomes in the patients, the preliminary results of its application have been promising.

No duplicate KRAS mutation is identified on the same allele in gastric or colorectal cancer cells with multiple KRAS mutations.

Codon 12 and 13 mutations in 170 colorectal cancer (CRC) and 66 gastric cancer (GC) specimens were analysed by an 'enriched' polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. All identified mutations were verified by direct sequencing of the second PCR products. Among the 170 CRC specimens, mutations were identified in 47 (28%) and 13 (7.6%) cases in codons 12 and 13, respectively. In the 66 GC specimens examined, however, mutations in codons 12 and 13 were only detected in two (3.0%) and one (1.5%) cases, respectively. Mutations in both codon 12 and 13 were found in 3/170 (1.8%) CRCs and 1/66 (1.5%) GCs. Duplicate mutations were never identified in the same allele, which was confirmed by direct sequencing of the second amplified products. The majority of colorectal and gastric cancer cells with KRAS mutations are homogeneous because they have the same KRAS mutation. A few colorectal or gastric cancers, however, showed heterogeneity, as verified by the fact that single mutations were identified in the same allele.

Predicting struvite formation for phosphorus recovery from human urine using an equilibrium model.

Interest in phosphorus recovery from urine diverted from faeces has been growing recently. Phosphorus in urine can be precipitated out as struvite (MgNH4PO4 x 6H2O) with addition of magnesium salt under alkaline conditions. Struvite formation, however, should be more well understood for its practical application. We predicted the struvite formation with a development of a new equilibrium model. The model considered the formation of eight different kinds of precipitates, including struvite, with effects of ionic strength and temperature. In addition, experiments on struvite formation in urine were conducted for the model validation. The model prediction of struvite formation had good agreement with the experimental results. The optimum pH to form struvite was predicted to be 9.4-9.7. In order to precipitate 99% of phosphate in urine with 1.5 fold Mg concentration to PO4-P, the pH value was necessary to be more than 8.1 based on the model prediction.

Interleukin 4 and gamma-interferon may play a role in the histopathogenesis of peripheral T-cell lymphoma.

The first demonstration of cytokine expression in T-cell lymphoma by immunohistochemical methods is reported. Lymph node biopsy specimens were obtained from 18 patients with peripheral T-cell lymphoma. Interleukin 4 (IL-4) and gamma-interferon were each detected in 7 lymph nodes. Lymph node specimens diagnosed as angioimmunoblastic T-cell lymphoma and angiocentric lymphoma having distinctive histopathological features expressed IL-4 more frequently than other T-cell lymphomas, and all 7 patients expressing IL-4 had hypergammaglobulinemia. Lymph nodes with gamma-interferon expression showed an increase in histiocytes and/or epithelioid cells. Thus, IL-4 may play an important role in the development of hypergammaglobulinemia as well as in the growth and histopathogenesis of T-cell lymphoma, and gamma-interferon may be responsible for the development of Lennert's lesion.

Isolation and characterization of proteoglycans from human nonepithelial tumors.

Proteoglycans (PGs) and glycosaminoglycans (GAGs) were identified in myogenic and fibrogenic tumors. More PGs containing mainly chondroitin sulfate could be detected in malignant tumors (leiomyosarcomas) than in benign tumors (leiomyomas and fibromas). Two groups of PGs were detected in the malignant tumors by ion-exchange chromatography and gel chromatography. One group was a large molecule with chondroitin sulfate side chains, seemingly composed of two or more subpopulations that were eluted from Sepharose CL-4B with a kav of 0.45. After removal of GAG side chains from the PG by chondroitinase AC digestion, core molecules with molecular weights greater than 200,000 were obtained. Another PG detected was a fraction of small PG eluted from Sepharose CL-4B with a kav of 0.45. It consisted of a core molecule with a molecular weight approximately equal to 48,000 and GAG side chains containing chondroitin sulfate-dermatan sulfate hybrids. The mixed sequence of L-iduronic acid with D-glucuronic acid in the same GAG chain was demonstrated by the formation of a small proportion of tetrasaccharide after chondroitinase AC digestion. In the benign tumors, the large PG was found only in very small amounts, and PG detected was composed mainly of the small one eluted from Sepharose CL-4B with a kav of 0.45. Its core protein had a molecular weight of approximately equal to 46,000, which was similar to that of small PG obtained from leiomyosarcomas, but its GAG side chains were composed mainly of dermatan sulfate containing small amounts of glucuronic acid. The results suggest that the core molecules of small PGs from both benign and malignant tumors are the products of the same gene but that they are processed in a different manner to form proteoglycans with different types of GAG chains.

High frequency of low-level microsatellite instability in early colorectal cancer.

Molecular events in early colorectal cancers (CRCs) have not been well elucidated because of the low incidence of early CRCs in clinical practice. Therefore, we studied 104 sporadic early CRCs with invasion limited to submucosa compared with 116 advanced CRCs. Loss of heterozygosity as well as microsatellite instability (MSI) status was examined. A significantly high frequency of low-level MSI (MSI-L) phenotype was detected in early CRCs (51.0%) compared with advanced CRCs (25.9%; P = 0.0001). In early and advanced CRCs, samples with MSI-L phenotype differed from microsatellite stable (MSS) phenotype with respect to loss of heterozygosity at 1p32 and 8p12-22. MSI-L is a frequent genetic event in early CRCs and may be a novel pathway in colorectal carcinogenesis distinct from both MSI-H and MSS.

Genetic alterations of candidate tumor suppressor ING1 in human esophageal squamous cell cancer.

Overexpression of ING1, a candidate tumor suppressor gene, efficiently blocks cell growth or induces apoptosis in different experimental systems. ING1 maps to chromosome 13q33-34, and because loss of the terminal region of chromosome 13q has been implicated in esophageal squamous cell cancer (ESCC), we examined ESCC for genetic alterations of ING1. Among 31 informative cases of ESCC, 58.9% of the tumors showed allelic loss at chromosome 13q33-34, and we detected four tumor-specific missense nucleotide changes. These alterations were found within the PHD finger domain and nuclear localization motif of the ING1 and may be functionally involved in the development of ESCC. Because immunohistochemical study revealed that all of the ESCC samples showed loss of ING1 protein expression, genetic or epigenetic alterations that abrogate the normal function of ING1 may contribute to esophageal squamous cell carcinogenesis.