Clinicopathological Variables Of Patients Research Articles

Lack of Increased P15INK4BProtein Expression in Basal Cell Carcinomas

The basal cell carcinoma (BCC) is the most common non-melanoma skin cancer (NMSK). BCC might develop because of the faulty cell cycle arrest. P15INK4b is a tumor suppressor gene, involved in cell cycle arrest and inactivated in most human cancers. The role of p15INK4b protein expression in the genesis of BCC is as yet unknown. In a previous study we showed the absence of p15INK4b expression in the majority of tissue microarray cores of cutaneous squamous cell carcinoma (SCCs), another type of non-melanoma skin cancer, indicating that p15INK4b could possibly be involved in the pathogenesis of cutaneous SCC. The aim of this study was to investigate p15INK4b protein expression in BCCs. Protein expression of p15INK4b in 35 cases of BCC tissue arrays and 19 cases of normal human skin tissue was studied using an immunohistochemical approach. The expression of p15INK4b was not significantly different in the BCC cases as compared with normal human skin (p=0.356; p>0.05). In addition, there were no significant relationship between clinicopathologic variables of patients (age and sex) and p15INK4b protein expression. Our finding may indicate that p15INK4b protein expression does not play a role in the genesis of BCC.

Pair-Box (PAX8) protein-positive expression is associated with poor disease outcome in women with endometrial cancer

Background:The Pax8 transcription factor genes have a role in cell differentiation and cell growth, and silencing of Pax8 in cell cultures results in cell death. The aims of this study were to determine the expression and correlation of Pax8 protein with several clinicopathological variables in patients with endometrial cancer.Methods:The following clinical parameters from 229 patients were used for correlation with Pax8 expression; age, histological subtype, myometrial depth of invasion, lymphovascular invasion (LVI), the International Federation of Gynecology and Obstetrics grade, lymph nodes status, and disease status.Results:A positive association of Pax8+ expression was found with high tumour grade (P=0.002), LVI+(P=0.0186), and type II tumour subtype (P<0.0001) in univariate analysis. Survival analysis showed an association of Pax8 and 5-year overall survival probability (P=0.01486), 80.04% for patients with Pax8− and 55.59% for patients with Pax8+. There was also an association of Pax8 and 5-year disease-free survival probability (P=0.02028), 72.12% for patients with Pax8− vs 49.88% for patients with Pax8+. Finally, an association of Pax8+ and shorter recurrence-free survival was also found (P=0.00203), with 74.36% for Pax8− and 52.11% for Pax8+.Conclusion:Overexpression of Pax8 protein by endometrial cancer is associated with poor disease outcomes. Inhibition of Pax8 may be a very attractive targeted therapy for selective patients.

Pattern of expression of cyclooxygenase-2 in malignant transformation of sinonasal inverted papilloma

ObjectiveCyclooxygenases (COXs) are enzymes that catalyze the conversion of arachidonic acid to prostaglandins. Many studies have suggested that COX-2, the inducible form of COX, is important in carcinogenesis. However, little is known about the pattern of expression of COX-2 in a multistep process of malignant transformation of sinonasal inverted papilloma (IP). In this study, we investigated COX-2 expression in IPs, IPs with dysplasia, IPs with squamous cell carcinoma (SCC), and primary SCCs of sinonasal tract. Study designA retrospective study was conducted. SettingThe setting was a tertiary care referral center. Subjects and methodsThe expression of COX-2 was evaluated by immunohistochemistry in 56, 7, 18, and 17 cases of IPs, IPs with dysplasia, IPs with SCC, and primary SCCs, respectively. Furthermore, we investigated the possible correlation between the expression of COX-2 and clinicopathologic variables in patients with IPs with SCC and primary SCC patients. ResultsPositive immunoreactivity for COX-2 was observed in 3 (5.4%) of 56 IPs, 7 (38.9%) of 18 IPs with SCC, and 7 (41.2%) of 17 primary SCCs, whereas it was not observed in IPs with dysplasia. The percentage of tumors with COX-2–positive immunostaining was significantly higher in IPs with SCC and primary SCCs compared with benign IPs. There was no significant correlation between the expression of COX-2 and clinicopathologic variables, such as tumor stage, histologic differentiation, and the proportion of malignant areas in patients with IPs with SCC. ConclusionCyclooxygenase-2 may play an important role in the process of malignant transformation from IP to SCC.

Resistin expression in breast cancer tissue as a marker of prognosis and hormone therapy stratification

ObjectiveAdipocytokines are adipocyte-derived hormones and well documented to be involved in carcinogenesis. The expression of resistin, a newly discovered adipocytokine, in breast cancer tissues was determined and correlated with patient clinicopathological variables. MethodsResistin expression in breast cancer tissues and the normal adjacent breast tissues was analyzed by immunohistochemistry and was correlated with clinicopathological variables as well as recurrence rates by the chi-square test. The prognostic value of resistin for disease-free and overall survival was determined by Kaplan–Meier estimates, and the significance of differences between curves was evaluated by the log-rank test. ResultsHigh resistin expression was predominantly observed in breast cancer tissues but not the adjacent normal breast tissues. High resistin expression in breast cancer tissues was correlated significantly with tumor stage, tumor size, lymph node metastasis and estrogen receptor status. Hormone therapy, but not radiotherapy or chemotherapy, decreased the recurrence rate in patients with high resistin expression. While high resistin expression was associated with poor disease-free and overall survival, Cox regression analysis also revealed that resistin was an independent predictor of disease-free and overall survival. ConclusionsHigh resistin expression in breast cancer tissue is associated with a more malignant clinicopathological status as well as poor patient survival. Resistin may therefore hold promise as an independent prognosis predictor for breast cancer, as a marker for hormone therapy stratification and as a potential therapeutic target.

HPV status in relation to clinicopathologic variables in patients with penile cancer at Los Angeles County-USC Medical Center.

329 Background: Penile squamous cell carcinoma (PSCC) is a disfiguring and deadly disease. US cancer registry reports a higher incidence in certain minority communities including those over-represented at LAC-USC. Human papilloma virus (HPV) infection is strongly associated with PSCC. This study examined correlations of HPV presence and subtype with PSCC patient clinicopathological variables. Methods: After IRB approval, a retrospective review of PSCC patients at LAC-USC between 1996-2010 was completed. HPV presence and genotype was detected from primary tumors of 33 patients by DNA amplification followed by reverse line blot hybridization. Associations with patient and tumor characteristics were examined by contingency analyses. Results: 20 (60.6%) patients were HPV+, and 85% of all HPV+ cases harbored at least one high-risk viral strain (80% of all positive cases had HPV 16, 5% HPV 31, 10% HPV 66). 20% of all positive cases harbored low-risk HPV 11; HPV strains 6 or 35 were not detected in any specimen. 3 patients were positive for multiple strains. Overall median age at diagnosis was 53 (range: 24-77) yrs. Median age was 56 yrs and 49 yrs for HPV+ and HPV- patients, respectively. HPV infection showed a trend towards being more prevalent in patients beyond the fifth decade of life, although this did not reach statistical significance (p=0.10). 22 (66.7%) patients were Hispanic; this ethnicity comprised 60% and 77% of HPV+ and HPV- cases, respectively (p=0.31). This cohort included Stage 0 (n= 1, n= 0), Stage 1 (n= 4, n=2), Stage 2 (n= 4, n= 4), Stage 3 (n=5, n= 1), and Stage 4 (n= 4, n= 5) HPV+ and HPV- patients, respectively. Neither HPV status nor presence of nodal metastasis was significantly associated with stage (p=0.50, p=0.52 respectively). Tumor grade was available for 30 (90.9%) cases; while HPV+ cases tended to have higher proportion of moderately-poorly differentiated tumors than HPV- cases (77.8% vs. 58.3%), this was not statistically significant (p=0.32). Conclusions: An overwhelming majority of HPV+ cases harbored at least one high-risk viral strain. Several interesting associations of HPV status with age and grade were noted, although the study was underpowered to show significance.

Highlights of This Issue

Visfatin, an adipocyte-secreted hormone, has been correlated with colorectal, prostatic, gastric, and esophageal cancers, but its role in breast cancer is not known. To address this question, Lee and colleagues examined the expression of visfatin in breast cancer tissues and correlated these results with patient clinicopathologic variables. High visfatin expression in breast cancer tissues was significantly correlated with tumor size, estrogen receptor (ER) negativity, and progesterone receptor (PR) negativity. In addition, worse disease-free and overall survival rates were observed when high visfatin expression was combined with ER- and PR-negative status. This study helps establish the prognostic significance of visfatin expression in breast cancer.Regular soy consumption has been associated with reduced breast cancer risk; however the mechanism of this hypothesized protection is not fully understood. To explore this possibility, Maskarinec and colleagues examined the effect of soy foods on estrogens in nipple aspirate fluid (NAF) and serum. Women were randomly assigned to high- or low-soy diets for 6 months, and estrogens in serum and NAF were examined. Mean estradiol and estrone sulfate levels were lower during the high-soy diet compared with the low-soy diet. The trend toward lower estrogens in NAF during a high-soy diet counters concerns about adverse effects of soy foods on breast cancer risk.Vitamin D compounds can inhibit prostate tumorigenesis in vitro, but epidemiologic data are inconsistent. In a nested case–control study, Albanes and colleagues examined the relationship between 25-hydroxyvitamin D [25(OH)D] and prostate cancer risk in Finnish men, ages 50 to 69 years. They found that men with higher vitamin D status, as determined by serum 25(OH)D concentrations, were at elevated risk of developing prostate cancer. No evidence was found for greater risk in men with low vitamin D status. These results suggest that caution is warranted with respect to recommendations for high-dose vitamin D supplementation.Allergic conditions are associated with reduced risk of several malignancies. In the Atherosclerosis Risk in Communities (ARIC) prospective cohort, Prizment and colleagues used blood eosinophil count, a marker for allergic disorders, to evaluate the association between colorectal cancer and allergy. The authors report an inverse association between blood eosinophil count and colorectal cancer risk that was not modified by age, sex, race, or smoking status. These novel findings support the hypothesis that allergies are protective for colorectal cancer.

High Visfatin Expression in Breast Cancer Tissue Is Associated with Poor Survival

Adipocytokines, adipocyte-secreted hormones, play a critical role in breast cancer development. The expression of visfatin, a newly discovered adipocytokine, in breast cancer tissues was determined and correlated with patient clinicopathologic variables. Visfatin expression in breast cancer tissues was analyzed by immunohistochemistry. Visfatin expression was correlated with clinicopathologic variables as well as recurrence rates, using the χ(2) test. The prognostic value of visfatin for disease-free and overall survival was evaluated by Kaplan-Meier estimates, and the significance of differences between curves was evaluated by the log-rank test. High visfatin expression in breast cancer tissues was significantly correlated with tumor size, estrogen receptor (ER) negativity, and progesterone receptor (PR) negativity. Hormone therapy, but not radiotherapy or chemotherapy, decreased the recurrence rate in patients with high visfatin expression. Whereas high visfatin expression alone was associated with poor disease-free and overall survival, worse disease-free and overall survival was observed when high visfatin expression was combined with ER- and PR-negative status. Cox regression analysis also revealed that visfatin is an independent predictor of disease-free and overall survival. High visfatin expression in breast cancer tissue is associated with more malignant cancer behavior as well as poor patient survival. Visfatin is an independent prognosis predictor for breast cancer.

Prognostic utility of β-tubulin isotype III and correlations with other molecular and clinicopathological variables in patients with early breast cancer: a translational Hellenic Cooperative Oncology Group (HeCOG) study

We evaluated the prognostic and predictive utility of β-tubulin isotype III (TUBB3) tumour gene transcription in early breast cancer patients enrolled in a randomised study. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was applied for assessment of TUBB3, ER, PgR, HER2 and MAPT messenger RNA and immunohistochemistry (IHC) for protein expression in 314 patients enrolled in trial HE10/97, evaluating epirubicin-alkylator adjuvant chemotherapy with or without paclitaxel. High TUBB3 mRNA status was associated with advanced T stage, high histological grade, low mRNA and protein levels of ER, PgR and MAPT, and high levels of HER2 (p < 0.001). At a median follow-up of 98 months, multivariate analysis showed high TUBB3 mRNA status to have prognostic significance for DFS (HR = 1.83, 95% CI 1.25-2.68, p = 0.002) and OS (HR = 1.71, 95% CI 1.03-2.83, p = 0.038), along with the number of involved axillary nodes, PgR mRNA status and tumour grade. TUBB3 mRNA levels did not predict benefit from inclusion of paclitaxel in adjuvant chemotherapy (test for interaction p = 0.96 for OS, p = 0.46 for DFS). Transcriptional activity of β-tubulin isotype III in early breast cancer is an adverse prognostic factor, though not a predictive one for taxane efficacy.

Pattern of Expression of Cell Cycle–related Proteins in Malignant Transformation of Sinonasal Inverted Papilloma

It has been suggested that sinonasal inverted papilloma (IP) can progress to squamous cell carcinoma (SCC); however, mechanisms of malignant transformation are not fully understood. This study investigated alterations in the expression of cell cycle-related proteins in a multistep process of malignant transformation of IPs. The expression of cell cycle-related proteins, including p53, p21, p16, and p63, was evaluated by immunohistochemistry in 21, 56, 7, and 18 cases of nasal polyps, IPs, IPs with dysplasia, and IPs with SCC, respectively. Furthermore, we determined the possible correlation between the expression of these proteins and clinicopathological variables in patients with IPs with SCC. Expression of p53 was found only in 8 of 18 IPs with SCC (44.4%). The frequency of p21 positivity was significantly higher in IPs with dysplasia (71.4%) and IPs with SCC (77.8%) compared with nasal polyps (0%) and IPs (12.5%). A p16 positivity was observed in 82.1% of IPs and 57.1% of IPs with dysplasia, whereas 83.3% of IPs with SCC showed an apparent loss of p16 protein expression. A p63 positivity was found in all specimens, but the percentage of positive cells was significantly increased in IPs with dysplasia and IPs with SCC compared with nasal polyps and IPs. There was no significant correlation between the expression of these proteins and clinicopathological variables, such as tumor stage, histological differentiation, and the proportion of malignant areas in patients with IPs with SCC. Alteration of cell cycle-related proteins may contribute importantly to the malignant transformation from IP to SCC.

PlGF expression in pre‐invasive and invasive lesions of uterine cervix is associated with angiogenesis and lymphangiogenesis

Most vascular endothelial growth factors (VEGF) have been shown to be associated with lymphangiogenesis and angiogenesis in various cancers. However, whether placental growth factor (PlGF), a rarely mentioned VEGF member, is involved in the pathogenesis of uterine cervical lesions remains unclear. To address this issue, we examined the relationship between PlGF expression and clinicopathologic variables in patients with pre-invasive and invasive lesions of uterine cervix. Sixty-two cervical specimens were immunostained with PlGF polyclonal antibody to define PlGF expression, and monoclonal antibodies D2-40 and CD34 to evaluate the lymphatic vessel density (LVD) and blood vessel density (BVD) of the lesions. PlGF mRNA level was detected by RT-PCR in all lesions from fresh tissues. We found that the levels of PlGF protein and mRNA expression were related to clinical stages (p < 0.05), but not to other clinicopathologic variables. No significant difference in PlGF expression was observed between squamous carcinoma and adenocarcinoma. Increased LVD and BVD were all associated with advanced stages (p < 0.001). Although LVD was strongly correlated with BVD, only high LVD was associated with pelvic lymphatic metastasis. Moreover, the level of PlGF expression was associated with both BVD(r = 0.715, p < 0.001) and LVD(r = 0.321, p < 0.05). Together, our study suggests that PlGF may participate in both tumor-associated angiogenesis and lymphangiogenesis of cervical carcinogenesis.

Activation of the mammalian target of rapamycin signalling pathway in prostate cancer and its association with patient clinicopathological characteristics

To evaluate the activation level of the mammalian target of rapamycin (mTOR) signalling pathway in Chinese patients with prostate cancer, as this pathway is over-activated in many human cancers and is an attractive target for cancer therapy. We used immunohistochemistry to investigate the activation level of five important markers of the mTOR pathway, including PTEN, p-Akt, p-mTOR, p-p70S6K and p-4E-BP1, in tissues from 182 patients with prostate cancer, 20 with benign prostatic hyperplasia (BPH) and 10 with high-grade prostatic intraepithelial neoplasia (HGPIN). The expression levels of these five markers were associated with patient clinical and pathological characteristics. Expression levels of p-Akt, p-mTOR, p-4E-BP1 and p-p70S6K were significantly higher in prostate cancer tissues than in BPH and HGPIN tissues. In 182 patients with prostate cancer the p-mTOR expression level significantly and positively correlated with its upstream p-Akt and downstream p-4E-BP1 and p-p70S6K expression levels. The cancer Gleason score was significantly correlated with p-Akt and p-mTOR expression level but not with p-4E-BP1 and p-p70S6K expression level. However, the p-4E-BP1 and p-p70S6K expression levels in primary cancer lesions were statistically significantly correlated with patient T stage and distant metastases. Most patients with prostate cancer have at least one component of the mTOR signalling pathway activated. The activation of the mTOR pathway might be involved in prostate cancer development and progression. The association between activation of mTOR pathway and patient clinicopathological variables suggested that not all patients are equally amenable to treatment strategies targeting the mTOR pathway.

Microsatellite analysis of allelic imbalance in tumour and blood from patients with prostate cancer

To investigate whether a high frequency of allelic imbalance (AI) is associated with clinicopathological variables of patients with prostate cancer. We analysed loss of heterozygosity (LOH) and microsatellite (MS) instability (MSI) on circulating plasma DNA in a polymerase chain reaction (PCR)-based MS study of 230 patients with prostate cancer and 43 with benign prostatic hyperplasia (BPH) using a panel of 13 polymorphic MS markers. The overall incidence of AI was significantly higher in primary tumours (34%) than in blood plasma samples from patients with prostate cancer (11%). Although LOH (2.0%) and MSI (1.5%) were also found in BPH plasma samples, their frequencies were low. AI identified in plasma samples from patients with prostate cancer could be retrieved in 63% of the paired tumour samples. The highest concordance of AI and retention of heterozygosity between tumour and plasma samples was 83% at the marker D8S360. There were high frequencies of LOH at the markers THRB, D7S522 and D8S137 in both types of specimens. The markers D11S898 and D11S1313 on the chromosome arm 11q showed frequent MSI. The comparison with established risk factors showed significant associations of an increase in prostate volume with AI at the combined markers D6S474/D7S522 in tumour tissues and at D7S522 in plasma samples (P < 0.04). In the primary tumours there was a further correlation of LOH at D11S1313 with increasing tPSA value (P = 0.005). The combination of total prostate-specific antigen (PSA) and % free PSA was associated with LOH at THRB in plasma samples. Plasma-based MS analysis may have clinical value for the molecular staging of prostate cancer.

Caveolin-1 and Ki-67 Expression as Prognostic Factors in Clear Cell Carcinoma of the Kidney

Purpose: Caveolin-1 is proposed to represent a novel tumor suppressor protein and expression of recombinant caveolin-1 is sufficient to restrict the growth potential of transformed cells isolated from primary tumors of the breast, lung, and ovaries. We examined the relationship of caveolin-1 and Ki-67 expression to clinicopathological variables in patients with clear cell carcinomas of the kidney. Materials and Methods: We examined caveolin-1 and Ki-67 expression in 119 clear cell carcinomas of the kidney using immunohistochemistry, and analyzed its relationship with tumor size, nuclear grade, TNM stage, vascular invasion, capsular invasion, metastasis, and metachronous metastasis were investigated. Results: Of the 119 tumors analyzed, lymph node and distant metastasis (synchronous metastasis: 7, metachronous metastasis: 15) occurred in 3 and 22 cases, respectively. Caveolin-1 expression correlated with the T stage (p=0.004), TNM stage (p=0.013), metastasis (p=0.013), and metachronous metastasis (p=0.001). Ki-67 expression correlated with the T stage (p=0.041), nuclear grade (p=0.011), and vascular invasion (p=0.043). Caveolin-1 and Ki-67 expression showed similar changes, but there was no statistical significance (p=0.050). Conclusions: Caveolin-1 is expressed frequently in patients with metachronous metastasis, and may predict metastasis after surgery for clear cell carcinoma of the kidney. (Korean J Urol 2008;49:99-106) 󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏

Role of fragile histidine triad protein expression in pathogenesis of malignant pleural mesothelioma

To investigate the relationship of fragile histidine triad (FHIT) and Ki-67 expression with clinicopathological variables of patients with malignant pleural mesothelioma (MPM). Formalin-fixed, paraffin-embedded tissue sections of 30 asbestos induced MPM (epithelial and biphasic) patients were examined for FHIT and Ki-67 expression using immunohistochemical techniques and results were compared with clinicopathological variables. Immunohistochemical study results were as follows: 12 (40%) cases showed low FHIT expression and 18 (60%) showed high expression. There was no significant relationship between FHIT and age, gender or histological subtypes (p > 0.05). Ki-67 expression was 'low' in 13 (43.3%) cases and 'high' in 17 (56.7%) cases. No correlation could be demonstrated between Ki-67 expression and age, gender or histological subtypes (p > 0.05). No significant association was observed between FHIT and Ki-67 expression in MPM. The results support the role of FHIT as a tumour suppressor gene in asbestos induced MPM. There is no significant correlation between FHIT and cell proliferation marker expressions in malignant pleural mesothelioma. Therefore, it can be concluded that loss of FHIT does not interfere with tumour proliferation. This can be accepted as evidence for an early role of FHIT loss in carcinogenesis; however, it needs to be strengthened by further studies.

Preoperative elevation of serum C – reactive protein is predictive for prognosis in myeloma bone disease after surgery

We investigated whether preoperative levels of serum C-reactive protein (CRP) and its correlation with tumour clinicopathological findings adds prognostic information beyond the time of diagnosis in patients with myeloma bone disease (MM) to facilitate the surgical decision-making process. Six hundred and fifty-eight myeloma patients were evaluated retrospectively for surgery. Clinicopathological variables of patients who underwent surgery (n=71) were compared between patients with preoperative CRP ⩾6 mg l−1 and those with CRP <6 mg l−1. Univariate and multivariate analyses were performed to identify prognostic factors after surgery. Patients with an increase of CRP prior to surgery showed inferior survival compared to patients with normal levels. Patients with normal CRP levels at diagnosis but elevations prior to surgery do seem to have a similar unfavourable overall survival (OS) than patients with an increase both, at diagnosis and at surgery. Conversely, patients with normal CRP levels prior to surgery still have the best OS, irrespective of their basic values. Multivariate analysis revealed preoperative CRP levels above 6 mg l−1 Lactate dehydrogenase (LDH) above normal, and osteolyses in long weight bearing bones as independent predictors of survival. These findings suggest that in patients with MM serum levels of CRP increase during disease activity and might be significantly correlated with specific disease characteristics including adverse prognostic features such as osteolyses in long weight bearing bones. Thus, preoperative elevated CRP serum levels might be considered as independent predictor of prognosis and could provide additional prognostic information for the risk stratification before surgical treatment in patients with myeloma bone disease.

Predictability of retroperitoneal lymph node metastasis by using clinicopathologic variables in surgically staged endometrial cancer

The purpose of this study was to predict lymphatic involvement in endometrial cancer using clinicopathologic variables of patients treated with surgical staging. Overall, 461 patients treated with an initial surgical staging procedure including complete pelvic-para-aortic lymphadenectomy were included. The mean number of resected lymph nodes was 27 (median 26; range 15-83), and 54 patients (12%) had lymphatic involvement. Of these patients, 32 had only pelvic, 15 had both pelvic and para-aortic, and 7 had isolated para-aortic metastases. In the multivariate analysis, deep myometrial invasion (P= 0.02), lymphvascular space invasion (P= 0.001), positive peritoneal cytology (P= 0.002), and cervical involvement (P= 0.003) predicted retroperitoneal lymph node metastasis (RLN) significantly. Two hundred seventy-four patients (59.4%) had at least one of these poor prognostic factors identified by multivariate analysis. In this patient population, 53 (19.3%) had lymphatic involvement compared to 1 patient in the group of 187 patients with low-risk criteria. Ninety-eight percent of patients with RLN were predicted by this model, and with the advent of accurate diagnostic techniques, 40% of patients could be saved from undergoing lymphadenectomy.

A single‐nucleotide polymorphism in the XPG gene, and tumour stage, grade, and clinical course in patients with nonmuscle‐invasive neoplasms of the urinary bladder

To evaluate whether the single nucleotide polymorphism (SNP), Asp1104His (G3507C), in the XPG gene affects malignant phenotypes of nonmuscle-invasive urinary bladder neoplasms (NIBN), by investigating associations between the SNP and clinicopathological variables in patients with NIBN. The 233 patients constituted newly diagnosed cases of primary NIBN in the Stockholm area. The Asp1104His polymorphism in the XPG gene was genotyped using a polymerase chain reaction-restriction fragment length polymorphism technique. The GC + CC genotypes were more frequent in stage pT1 tumours at initial diagnosis than pTa (odds ratio 1.9, 95% confidence interval 1.0-3.5, P = 0.048). The difference was larger in the young group (4.6, 1.9-11.8, P = 0.001). In the young group, the GC + CC genotypes were significantly more frequent in high-grade than in low-grade tumours (3.1, 1.5-6.8, P = 0.004) whereas in the older group the genotypes were less frequent in high-grade tumours (0.3, 0.1-0.7, P = 0.007). The XPG genotypes were not associated with tumour recurrence, stage progression or survival. These results suggest that the SNP in the XPG gene might be related to tumour invasiveness in NIBN.

Invasive potency related to RCAS1 expression in uterine cervical cancer

Objectives. RCAS1 expression is significantly associated with clinical prognosis in various human cancers, which suggests that RCAS1 may be involved in acquisition of malignant phenotypes. To investigate the relationship between RCAS1 and one such characteristic, tumor invasiveness, we examined RCAS1 expression in cervical neoplasms ranging from the precancerous state to invasive cancer. Methods. RCAS1 expression was studied retrospectively via immunohistochemical methods. Samples consisted of biopsy tissue from 90 patients with intraepithelial neoplasia and resected tumor tissue from 154 patients with invasive cancer. Statistical analysis was done to correlate RCAS1 expression and clinicopathologic variables in patients with a depth of cancer cell invasion into stromal tissue of >5 mm. Results. RCAS1 expression was detected in patients with intraepithelial cancer and invasive cancer but not in patients with dysplasia. The occurrence and degree of RCAS1 expression increased with the depth of invasion. In patients with invasive cancer, RCAS1 overexpression was significantly correlated with invasion of the lymph-vascular space, lymph node metastasis in two or more sites, and tumor volume; RCAS1 expression was not associated with histologic subtype. Overall survival rates for patients with RCAS1 overexpression were significantly shorter than those for patients without RCAS1 overexpression. In connective tissue surrounding tumor cells, the number of cells expressing vimentin significantly decreased in relation to RCAS1 expression level. Moreover, significant associations between expression levels of RCAS1 and those of MMP-1 and laminin-5 were found. Conclusion. RCAS1 may contribute to acquisition of malignant uterine cervical phenotypic characteristics including invasion, metastasis, and tumor growth via connective tissue remodeling.

Recurrence and prognostic factors in borderline ovarian tumors

Objective. The purpose of this study was to evaluate the survival estimates and clinico-pathological variables in patients treated for borderline ovarian tumors. Methods. The patients treated for borderline ovarian tumors were evaluated retrospectively. Data were obtained from hospital records and special gynecologic oncology forms. Results. Overall, 100 patients were evaluated. The mean age at the time of diagnosis was 41.7 (range, 19–84). Seventy one (71%) patients underwent surgical staging including 49 (49%) of them with comprehensive surgical staging, 22 (22%) with fertility-sparing surgery. Only 30 (30%) patients were unstaged. The histopathological diagnosis was serous, mucinous, and the other types of borderline ovarian tumor in 54 (54%), 39 (39%), and 7 (7%) of the patients, respectively. Seventy patients had stage IA (70%), 10 had stage IB (10%), 9 had stage IC (9%), 3 had stage IIIA (3%), and 8 had stage IIIC (8%) disease. The stage of only four patients in which disease confined to ovary was upgraded as stage IIIC following surgical staging procedure. The recurrence rate was found 3% (3). The overall disease-free survival rates of BOT in surgically staged (comprehensive, fertility-sparing surgery) and unstaged patients were 97.92%, 95.00%, and 96.30%, respectively. But, the overall tumor-free survival was significantly found to be decreased in cases of young age (<30 years old), performing fertility-sparing surgery and presence of micropapillary architecture or peritoneal implants. Overall survival rates of BOT in surgically staged (comprehensive, fertility-sparing surgery) and unstaged patients were 97.9%, and 100% and 100%, respectively. Conclusion. Low malignant potential ovarian tumors have excellent survival, and the patients can be treated safely by conservative surgery.

Combined Evaluation of Expressions of Cyclin E and p53 Proteins as Prognostic Factors for Patients with Gastric Cancer

There is a lack of consistency regarding the prognostic value of cyclin E overexpression in gastric cancer (gastric cancer). Our aim was to report on this overexpression and to analyze its correlations with the clinicopathologic variables. Another aim was to examine if aberrant expression of both cyclin E and p53 might increase the malignant potential of gastric cancer. Specimens from 89 patients with gastric cancer treated with "curative" intent were evaluated for cyclin E and p53 expressions using immunohistochemical method. The correlations between cyclin E overexpression alone or in combination with p53 expression and the patient's clinicopathologic variables were analyzed. Cyclin E overexpression and p53 expression were shown in 35 (39.3%) and 46 (51.7%) tumors, respectively. The incidence of cyclin E overexpression was significantly higher in deeply invasive cancers (P < 0.0001), in cancers with lymph node metastasis (P = 0.003), and in cancers with advanced stages (P < 0.0001). There were no significant correlations with other clinicopathologic variables. Patients in whom their tumors showed cyclin E overexpression alone or in combination with p53 survived less than patients with negative cyclin E tumors. Multivariate analysis revealed that combined cyclin E overexpression and p53 expression was significantly associated with poor survival after adjusting for other variables (hazard ratio, 3.12; P = 0.009). Cyclin E overexpression is a common event in gastric cancer. Gastric cancer with cyclin E overexpression exhibit increased aggressiveness in the presence of aberrant p53. The combination of cyclin E overexpression with the p53 expression in gastric cancer further distinguished a subgroup of patients with poor prognosis.