[Invasive breast lobular carcinoma with extracellular mucin: a clinicopathological analysis].

Objective: To study the clinicopathological features of invasive lobular carcinoma (ILC) of the breast with extracellular mucin and outcomes of patients. Method: Clinicopathological features and clinical follow-up (39-123 months and a median follow-up of 55 months) of seven ILC with extracellular mucin were obtained. Hematoxylin-and-eosin (H&E) and immunohistochemistry (IHC) stained sections were reviewed, and fluorescence in situ hybridization (FISH) assay was performed for tumors with HER2 IHC 2+. Patient prognosis was analyzed and literatures related to ILC with extracellular mucin were reviewed. Results: All seven patients were female, aged from 43 to 73 years (median age, 55 years). The tumors ranged in size from 1 to 5 cm (median size 2 cm). All seven cases were of histological grade 2. Most areas of the tumors presented with the morphology of classic ILC, and variable amount of extracellular mucin were observed focally. In six cases, part of the tumor cells contained intracellular mucin, and the nucleus were pushed to one side of the cells, creating the impression of signet-ring cells. Two patients had lymph node metastases at diagnosis, and developed liver and bone metastases at 38th and 48th month, respectively, after surgery, and died at 48th and 123th month, respectively. While the other five patients, except one lost to follow-up, had been disease-free during the follow-up period. IHC results showed estrogen receptor (ER) and progesterone receptor (PR) positivity in 7/7 and 6/7 cases, respectively. Tumors of six patients were HER2 IHC 0/1+. The remaining one was HER2 IHC 2+, while FISH assay revealed HER2 gene amplification in that tumor. The proportion of cases with HER2-positivity was 1/7. The proliferation index Ki-67 ranged from less than 5% to 30%, and Ki-67 less than or equal to 10% were in 5/7 cases. According to the 2013 St. Gallen International Expert Consensus on breast cancer, all tumors were of luminal types; of those, two were luminal A and five were luminal B. Conclusions: ILC with extracellular mucin tends to occur in women over 50 years old. All tumors in the study are grade 2 classic ILC, with signet-ring cells as a common feature. All seven tumors are classified as luminal types, with luminal B as the main molecular subtype.

Eye Protection in Liver Transplantation Patients Under General Anesthesia.

BACKGROUND: Opsite (Smith & Nephew, Hull, UK) is widely used in wound care but its use in eye protection against corneal abrasion during major surgery is rarely reported. The purpose of the current study is to compare the effectiveness of using Opsite in eye protection with either wet gauze alone or with wet gauze following application of eye ointment in patients undergoing living donor liver transplantation (LDLT). METHODS: This is a prospective, double-blinded, randomized controlled trial. Forty-one patients undergoing liver transplantation were enrolled. One eye of each patient was protected with sterile gauze soaked with normal saline solution and covered with Opsite. Duratears (ALCON, Fort Worth, Tex, United States) ointment was applied to the other eye before covering it with sterile wet gauze and Opsite (ointment group). The corneal examination was carried out after fluorescein staining before and at the end of surgery by the same doctor. A Student t-test and a χ2 test were used for the statistical analyses. RESULTS: Forty-one patients with 82 eyes were observed in this study. No corneal epithelial defects were found in either the normal saline group or the ointment group. CONCLUSION: Opsite combined with wet gauze with or without additional eye ointment provided 100% protection against corneal abrasion in patients undergoing LDLT.

[Correlation between androgen receptor expression and surrogate molecular subtypes in invasive breast carcinoma].

Objective: To investigate androgen receptor(AR)expression in invasive breast carcinoma and the correlation with surrogate molecular breast carcinoma subtypes. Methods: Immunohistochemical staining of AR and other biomarkers was performed in a cohort of 870 cases of primary invasive breast carcinomas collected from August to December, 2016. The association of AR expression with different histological and surrogate molecular subtypes was analyzed. Results: The positive expression rate of AR in the immunohistochemistry-based surrogate subtypes was 96.3%(207/215) for Luminal A, 89.8%(378/421) for Luminal B, 82.4%(75/91) for HER2 overexpression and 37.1%(53/143) for triple negative breast carcinoma, with significant differences among the four groups (P<0.01). AR correlated positively with the expression of ER(P<0.01), PR(P<0.01), HER2(P=0.007), GATA3(P<0.01), GCDFP15(P<0.01)and mammaglobin(P<0.01), while negatively with the expression of Ki-67(P<0.01), CK5/6(P<0.01)and CK14(P<0.01). Conclusions: AR exhibits a high expression in invasive breast carcinoma, which is mainly correlated with ER-positive breast carcinoma. Regardless of the relatively low expression rate, AR is a potential therapeutic target in triple negative breast carcinoma.

Well-balanced commensal microbiota contributes to anti-cancer response in a lung cancer mouse model.

The intestinal microflora affects inflammation and immunity, not only locally at the mucosal level but also systemically, raising the question of whether the microflora affects inflammatory processes that contribute to cancer and its therapy. Prebiotics have also been found to play an antitumor role that is not limited to the gut. We investigated the antitumor roles of the intestinal microbiota using the Lewis lung cancer mouse model. In mice treated with cisplatin combined with ABX (an antibiotic cocktail of vancomycin, ampicillin, and neomycin), which can destroy the host commensal microflora, the tumor size was larger than in mice on a single treatment of cisplatin. Moreover, the survival rate of mice treated with cisplatin combined with ABX was significantly reduced. In contrast, mice treated with cisplatin combined with Lactobacillus bacteria had smaller tumors and an improved survival rate. Further study on gene expression indicated that ABX can partially impair the function of cisplatin by upregulating the expression of VEGFA and downregulating the expression of BAX and CDKN1B. The expression of IFN-γ, GZMB, and PRF1 in the CD8(+) T cells of these mice was reduced by ABX, indicating an immuno-enhancement role of commensal microbiota. Conversely, Lactobacillus co-treatment mice showed an enhanced antitumor response with upregulated IFN-γ, GZMB, and PRF1 expression. We conclude that the commensal microbiota contributes to the anti-lung cancer response and probiotics co-treatment can enhance the antigrowth and proapoptotic effects of cisplatin.

Alternatively spliced, truncated GCSF receptor promotes leukemogenic properties and sensitivity to JAK inhibition.

Granulocyte colony-stimulating factor (GCSF) drives the production of myeloid progenitor and precursor cells toward neutrophils via the GCSF receptor (GCSFR, gene name CSF3R). Children with severe congenital neutropenia chronically receive pharmacologic doses of GCSF, and ∼30% will develop myelodysplasia/acute myeloid leukemia (AML) associated with GCSFR truncation mutations. In addition to mutations, multiple isoforms of CSF3R have also been reported. We found elevated expression of the alternatively spliced isoform, class IV CSF3R in adult myelodysplastic syndrome/AML patients. Aside from its association with monosomy 7 and higher rates of relapse in pediatric AML patients, little is known about the biology of the class IV isoform. We found developmental regulation of CSF3R isoforms with the class IV expression more representative of a progenitor cell stage. Striking differences were found in phosphoprotein signaling involving Janus kinase (JAK)-signal transducer and activator of transcription (STAT) and cell cycle gene expression. Enhanced proliferation by class IV GCSFR was associated with diminished STAT3 and STAT5 activation, yet showed sensitivity to JAK2 inhibitors. Alterations in the C-terminal domain of the GCSFR result in leukemic properties of enhanced growth, impaired differentiation and resistance to apoptosis, suggesting that they can behave as oncogenic drivers, sensitive to JAK2 inhibition.

Mst1 overexpression inhibited the growth of human non-small cell lung cancer in vitro and in vivo.

Mammalian STE20-like kinase 1 (Mst1) ubiquitously encodes serine threonine kinase, which is a 59-kDa class II GC kinase that shares 76% identity in amino-acid sequence with MST2, and is the closest mammalian homolog of Drosophila Hippo protein kinase, a major inhibitor of cell proliferation in Drosophila. Recent studies have shown that Mst1 and Mst2 perform tumor-suppressor function in a redundant manner and were originally identified as pro-apoptotic cytoplasmic kinases important for controlling cell growth, proliferation, apoptosis and organ size. We used recombinant eukaryotic expression vector containing human wild-type Mst1 gene to transfect human non-small cell lung cancer (NSCLC) A549 cells in vitro and in vivo. The results showed that Mst1 overexpression inhibited cell proliferation and induced apoptosis of A549 cells, promoted Yes-associated protein (YAP) (Ser127) phosphorylation and downregulated the transcriptional level of Cystein-rich protein connective tissue growth factor (CTGF), amphiregulin (AREG) and Survivin. In human NSCLC-cell-A549-xenograft models, Mst1 gene or cisplatin alone suppressed the growth of tumors and increased the cytoplasm-positive expression levels of YAP and Phospho-YAP (Ser127) proteins; however, their combination had the strongest anticancer effects. Overall, Mst1 has an important role in inhibiting the growth of NSCLC in vitro and in vivo; its antiproliferative effect is associated with induction of apoptosis through promotion of the cytoplasmic localization and phosphorylation of YAP protein at Ser127 site, indicating that Mst1 may be developed as a promising therapeutic target for NSCLC.

The effect of pre-procedure anxiety on sedative requirements for sedation during colonoscopy.

This study investigated the effects of pre-procedural anxiety (assessed using the Beck Anxiety Inventory) on sedative requirements in 135 patients undergoing sedation for colonoscopy. Deep sedation was defined as loss of consciousness and no response to colonoscopy, and was achieved by target-controlled infusion of propofol. Patients' characteristics, baseline haemodynamic profiles, Beck Anxiety Inventory scores, effect-site propofol concentration at loss of consciousness and characteristics of recovery were recorded. No correlations were found between Beck Anxiety Inventory scores and effect-site propofol concentration at loss of consciousness or baseline haemodynamic profiles. There was no statistical difference in the characteristics of recovery among patients with different levels of anxiety. In conclusion, in patients receiving deep sedation for colonoscopies, the level of pre-procedural anxiety did not relate to the sedative requirement or post-procedural recovery characteristics.

Effect of university of wisconsin and histidine-tryptophan-ketoglutarate preservation solutions on blood potassium levels of patients undergoing living-donor liver transplantation.

BACKGROUND: The potassium content of University of Wisconsin solution (UW) is 125 mEq/L and that of histidine-tryptophan-ketoglutarate solution (HTK) only 9 mEq/L. The aim of the present study was to analyze their effects to change potassium levels on reperfusion among patients undergoing living-donor liver transplantation. METHODS: Anesthesia records of adult living-donor liver transplant patients were reviewed retrospectively. Patients received liver graft preserved in UW were grouped in group I (GI) and HTK in group II (GII). The potassium levels in the anheptic phase were compared with those 5 minutes after reperfusion using paired Student t tests. P values of <.05 were regarded to be significant. RESULTS: Eighty-five GI patients showed the potassium significantly decreased from 3.76±0.70 to 3.60±0.74, whereas the change among 355 GII patients was almost unremarkable: 4.00±0.57 to 3.96±0.06 mEq/L. CONCLUSIONS: Although UW contains a higher potassium content, it seems to have no negative impact on changes in serum potassium levels; in contrast it decreased the potassium level significantly at 5 minutes after reperfusion. Both preservation solutions maintain the patients' potassium levels within the normal range.

Capsaicin mediates apoptosis in human nasopharyngeal carcinoma NPC-TW 039 cells through mitochondrial depolarization and endoplasmic reticulum stress.

Capsaicin, a pungent compound found in hot chili peppers, has been reported to have antitumor activities in many human cancer cell lines, but the induction of precise apoptosis signaling pathway in human nasopharyngeal carcinoma (NPC) cells is unclear. Here, we investigated the molecular mechanisms of capsaicin-induced apoptosis in human NPC, NPC-TW 039, cells. Effects of capsaicin involved endoplasmic reticulum (ER) stress, caspase-3 activation and mitochondrial depolarization. Capsaicin-induced cytotoxic effects (cell death) through G0/G1 phase arrest and induction of apoptosis of NPC-TW 039 cells in a dose-dependent manner. Capsaicin treatment triggered ER stress by promoting the production of reactive oxygen species (ROS), increasing levels of inositol-requiring 1 enzyme (IRE1), growth arrest and DNA-damage-inducible 153 (GADD153) and glucose-regulated protein 78 (GRP78). Other effects included an increase in cytosolic Ca(2+), loss of the mitochondrial transmembrane potential (ΔΨ(m)), releases of cytochrome c and apoptosis-inducing factor (AIF), and activation of caspase-9 and -3. Furthermore, capsaicin induced increases in the ratio of Bax/Bcl-2 and abundance of apoptosis-related protein levels. These results suggest that ER stress- and mitochondria-mediated cell death is involved in capsaicin-induced apoptosis in NPC-TW 039 cells.

Anharmonic effect on unimolecular reactions with application to the photodissociation of ethylene.

The importance of anharmonic effect on dissociation of molecular systems, especially clusters, has been noted. In this paper, we shall present a theoretical approach that can carry out the first principle calculations of anharmonic canonical and microcanonical rate constants of unimolecular reactions within the framework of transition state theory. In the canonical case, it is essential to calculate the partition function of anharmonic oscillators; for convenience, the Morse oscillator potential will be used for demonstration in this paper. In the microcanical case, which involves the calculation of the total number of states for the activated complex and the density of states for the reactant, we make use of the fact that both the total number of states and the density of states can be expressed in the inverse Laplace transformation of the partition functions and that the inverse Laplace transformation can in turn be carried out by using the saddle-point method. We shall also show that using the theoretical approach presented in this paper the total number of states and density of states can be determined from thermodynamic properties and the difference between the method used in this paper and the thermodynamic model used by Krems and Nordholm will be given. To demonstrate the application of our theoretical approach, we chose the photodissociation of ethylene at 157 and 193 nm as an example.

Theoretical studies on tunneling ionizations from the doubly degenerate highest occupied molecular orbitals of benzene in intense laser fields.

Combining our generalized Keldysh theory [Sov. Phys. JETP 20, 1307 (1965)] with the molecular orbital theory, the authors theoretically study tunneling ionizations of neutral benzene in intense linearly polarized Ti:sapphire laser fields (800 nm). They consider the ionizations from the highest occupied molecular orbitals (HOMOs) of the ground electronic state. The double degeneracy of the HOMOs is properly taken into account. In the theory, molecular ionizations consist of the individual ionizations from each atom and the quantum interferences between them. The theory reproduces the experimental data well. The authors also show that the polarization dependence of the ionization rates is strongly influenced by the quantum interferences.

Micrometastases detected by cytokeratin 19 expression in sentinel lymph nodes of patients with early-stage cervical cancer.

The purpose of this study was to detect micrometastases in sentinel lymph nodes (SLNs) by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC) analyses for cytokeratin 19 (CK19) expression in early-stage cervical cancer. One hundred twenty-five SLNs were collected from 46 patients with early-stage cervical cancer. Conventional histopathologic techniques revealed 14 metastatic SLNs from 11 out of 46 patients. CK19 expression was detected by RT-PCR and IHC in all the 125 SLNs. Cervical cancer tissues from nine patients and five pelvic lymph nodes from the patients without tumor were utilized as positive and negative controls, respectively. All the metastastic SLNs on conventional histopathologic techniques were positive by either RT-PCR or IHC analyses, while all the positive controls were positive and all the negative controls were negative as expected. Of 35 patients without metastatic SLNs on conventional histopathologic techniques, the detection rate of micrometastases was 42.85% by RT-PCR and 20% by IHC analyses. RT-PCR and IHC were more sensitive to identify micrometastases in SLNs of patients with early-stage cervical cancer than routine pathology. These findings demonstrated that micrometastasis could be identified by molecular technique such as RT-PCR and IHC analyses for CK19 expression. RT-PCR was more sensitive to detect micrometastases in SLNs than IHC in patients with early-stage cervical cancer. Therefore, molecular assessment of the SLNs may be a valuable tool to complement routine histologic examination of cervical cancer. The importance of micrometastases in SLNs is under close clinical observation to determine whether it can be used as a predicting factor to help us make decision whether to proceed with whole-pelvic lymph node dissection or as a prognostic factor for clinical outcome.

Diallyl disulfide (DADS) induced apoptosis undergo caspase-3 activity in human bladder cancer T24 cells.

Diallyl disulfide (DADS), one of the major components of garlic (Allium sativum), is well known to have chemopreventative activity against human cancer such as colon, lung and skin. But the exact mechanism of the action is still unclear. In this study, we investigated how DADS--induced cell cycle arrest and apoptosis in T24 human bladder cancer cells in vitro. Apoptosis induction, cell viability, cell cycle arrest, caspases-3, -9 activity and gene expression were measured to determine their variation by flow cytometric assay, western blot, and determination of caspase-3 activity, PCR and cDNA microarray. There are significant differences in cell death (decreased viable cells then increased the amounts of apoptosis) of T24 cells that were detected between DADS (5-75 microM) treated and untreated groups. A significant increase was found in apoptosis induction when cells were treated with DADS (50 microM) compared to without DADS treated groups. DADS also promoted caspase-3 activity after exposure for 1, 3, 6, 12, and 24 h, which led to induce apoptosis. DADS also increased the product of intracellular hydrogen peroxide. Furthermore, the DADS-induced apoptosis on T24 cells was blocked by the broad-spectrum caspase inhibitor, z-VAD-fmk and antioxidant (catalase). DADS also increased cyclin E and decreased CDK2 gene expression which may lead to the G2/M arrest of T24 cells.

Inhibition of N-acetyltransferase activity and gene expression in human colon cancer cell lines by diallyl sulfide.

Diallyl sulfide (DAS) is one of the major components of garlic (Allium sativum) and is widely used in the world for food. In this study, DAS was selected for testing the inhibition of arylamine N-acetyltransferase (NAT) activity (N-acetylation of 2-aminofluorene) and gene expression (mRNA NAT) in human colon cancer cell lines (colo 205, colo 320 DM and colo 320 HSR). The NAT activity was examined by high performance liquid chromatography and indicated that a 24 h DAS treatment decreases N-acetylation of 2-aminofluorene in three colon (colo 205, 320 DM and colo 320 HSR) cancer cell lines. The NAT enzymes (protein) were analyzed by western blotting and flow cytometry and it indicated that DAS decreased the levels of NAT in three colon (colo 205, 320 DM and colo 320 HSR) cancer cell lines. The gene expression of NAT (mRNAT NAT) was determined by polymerase chain reaction (PCR), it was shown that DAS affect mRNA NAT expression in examined human colon cancer cell lines. This report is the first to demonstrate that DAS does inhibit human colon cancer cell NAT activity and gene expression.

The effect of paclitaxel on 2-aminofluorene-DNA adducts formation and arylamine N-acetyltransferase activity and gene expression in human lung tumor cells (A549).

In this study, paclitaxel was used to determine inhibition of arylamine N-acetyltransferase (NAT) activity, gene expression and 2-aminofluorene-DNA adduct formation in a human lung tumor cell line (A549). The activity of NAT was measured by HPLC assaying for the amounts of N-acetyl-2-aminofluorene (2-AAF) and remaining 2-aminofluorene (2-AF). Human lung tumor cell cytosols and intact cells were used for examining NAT activity and carcinogen-DNA adduct formation. The results demonstrated that NAT activity, gene expression (NAT1 mRNA) and 2-AF-DNA adduct formation in human lung tumor cells were inhibited and decreased by paclitaxel in a dose-dependent manner. The effects of paclitaxel on the values of the apparent Km and Vmax of NAT from human lung tumor cells were also determined in both examined systems. The result also indicated that paclitaxel decreased the apparent values of Km and Vmax from human lung tumor cells in both cytosol and intact cells. Thus, paclitaxel is an uncompetitive inhibitor to NAT enzyme.

Laparoscopic nephrectomy for inflammatory renal conditions.

PURPOSE: Inflammatory and infectious renal conditions may result in severe perirenal fibrosis, making the laparoscopic approach challenging. The theoretical advantages of laparoscopy for managing inflammatory and infectious renal conditions have been questioned. We identified whether laparoscopy for inflammatory renal conditions is associated with higher morbidity than for other benign renal conditions. Furthermore, several technical modifications are discussed that may help to improve the outcome. MATERIALS AND METHODS: We retrospectively reviewed the records of all patients who underwent laparoscopic nephrectomy for inflammatory and infectious renal conditions between 1998 and 2000. The transperitoneal approach was used and specimens were removed after morcellation. Operative data were compared with those from a similar group of patients who underwent laparoscopic nephrectomy for other benign conditions. RESULTS: Laparoscopic nephrectomy done for inflammatory or infectious conditions in 12 cases and for other benign conditions in 9 matched cases was completed successfully in 10 (83%) and 9 (100%), respectively. In the inflammatory and benign groups mean blood loss plus or minus standard deviation was 155 +/- 163 and 59 +/- 23 ml. (p = 0.099), mean operative time was 284 +/- 126 and 226 +/- 62 minutes (p = 0.225), and mean postoperative hospital stay was 4.1 +/- 2 and 3 +/- 1 days (p = 0.157), respectively. CONCLUSIONS: Laparoscopic nephrectomy can be performed safely in most cases of inflammatory renal conditions. Although they were not statistically significant, a higher conversion rate and longer operative time should be expected. Early conversion may be required due to failure to progress. Similar advantages were observed in patients with inflammatory and other benign renal conditions via the laparoscopic approach.

Transperitoneal preperitoneal laparoscopic lumbar incisional herniorrhaphy.

PURPOSE: Flank incisions may be associated with flank hernias, which may be complicated by incarceration and strangulation. Furthermore, they may be the cause of significant patient dissatisfaction with the surgical outcome. To avoid an open surgical procedure with its associated morbidity for hernia repair we describe a novel laparoscopic technique for repairing flank hernias with minimal morbidity and an excellent outcome. MATERIALS AND METHODS: Three cases of flank hernia were managed by the transperitoneal preperitoneal laparoscopic approach using polypropylene mesh to repair the fascial defect. An initial transperitoneal approach helps to identify the limits of the hernia. A 2 to 3 cm. margin of overlying peritoneum is incised around the hernia margin. It is important not to dissect overlying bowel. The mesh is placed behind the peritoneal envelope and secured with hernia staples. RESULTS: All cases were managed successfully via laparoscopy. There were no intraoperative or postoperative complications. At a mean followup of 12 months cosmesis has been excellent and there have been no recurrences. CONCLUSIONS: We describe a minimally invasive, versatile technique for laparoscopic repair of flank incisional hernias with excellent functional and cosmetic results. This approach avoids the significant morbidity associated with open repair of incisional flank hernias.

Clinicopathological and molecular genetic analysis of 4 typical Chinese HNPCC families.

AIM: To study the clinicopathological and molecular genetic characteristics of typical Chinese hereditary nonpolyposis cotorectal cancer (HNPCC) families. METHODS: Four typical Chinese HNPCC families were analyzed using microdissection, microsatellite instability analysis, immunostaining of hMSH2 and hMLH1 proteins and direct DNA sequencing of hMSH2 and hMLH1 genes. RESULTS: All five tumor tissues of 4 probands from the 4 typical Chinese HNPCC families showed microsatellite instability at more than two loci (MSI-H or RER+ phenotype). Three out of the 4 cases lost hMSH2 protein expression and the other case showed no hMLH1 protein expression. Three pathological germline mutations (2 in hMSH2 and 1 in hMLH1), which had not been reported previously, were identified. The same mutations were also found in other affected members of two HNPCC families,respectively. CONCLUSION: Typical Chinese HNPCC families showed relatively frequent germline mutation of mismatch repair genes. High-level microsatellite instability and loss of expression of mismatch repair genes correlated closely with germline mutation of mismatch repair genes. Microsatellite instability analysis and immunostaining of mismatch repair gene might serve as effective screening methods before direct DNA sequencing. It is necessary to establish clinical criteria and molecular diagnostic strategies more suitable for Chinese HNPCC families.

Lack of evidence for the association of tumor necrosis factor-alpha gene promoter polymorphism with calcium oxalate stone and bladder cancer patients.

Urinary stone disease and bladder cancer are two of the most commonly seen urologic diseases in Taiwan. Tumor necrosis factor-alpha (TNF-alpha) is one of the cytokines secreted by macrophages and is related to a sequence of events in response to inflammation and cancer formation. We investigated the polymorphism of the TNF-alpha gene promoter -308 as a genetic marker in searching for the association between these two commonly seen urologic diseases. One hundred and fourteen patients with transitional cell carcinoma of the urinary bladder and 103 patients with calcium oxalate stone were compared with 150 healthy controls. The polymorphism was detected by polymerase chain reaction-based restriction analysis (Nco I endonuclease). The results revealed no significant differences between normal individuals and the patients with the two commonly seen urologic diseases (P > 0.05). We concluded that the polymorphism of the TNF-alpha promoter -308 is not a valid genetic marker for these two urologic diseases.

Distributions of p53 codon 72 polymorphism in bladder cancer--proline form is prominent in invasive tumor.

Abnormal function of p53 is commonly associated with various cancer formations. High-grade and late-stage bladder cancers have been reported to have mutated or become inactive p53 when using immunohistochemical stains. Recently, p53 codon 72 polymorphism was extensively studied to determine the risk factors responsible for cancer formation. There was a general population of codon 72 sequence polymorphism of the wild type p53. A single base change from G to C caused the alteration of amino acid residue 72 from arginine to proline. The arginine form is considered to be a significant risk factor in the development of cancer. However, various reports had indicated discrepancies with regard to this polymorphism; some showed no significant difference between the control and cancer groups, while other series were associated with high risks in the proline form homozygotes. To resolve the undefined distribution of this polymorphism in bladder cancers, 58 patients with bladder cancer were enrolled onto this study. When checked using the Chi-squared test (P = 0.952) there were no differences between the control subjects and bladder cancer patients in the distribution of polymorphism. However, proline form homozygotes were more frequently found in the invasive group than the non-invasive group by Fisher's exact test (25% and 2.9%, respectively, P < 0.001). More than 70% of the non-invasive bladder cancers were the arginine form homozygotes. This result is consistent with those reported for hepatocellular carcinoma that showed a history of chronic liver disease and proline form homozygotes in a report by Yu et al. Our data suggest that proline form homozygotes are associated with invasive bladder cancer.