Does the expression of BCL2 have prognostic significance in malignant peritoneal mesothelioma?

Background Malignant peritoneal mesothelioma (MPM) is a rare neoplasm of the peritoneal membrane that is causally related to asbestos exposure. Survival after treatment is poor. Current therapy involving hyperthermic intraperitoneal chemotherapy has improved survival in selective patients. In the past, several prognostic factors have been identified in MPM patients and this has prompted the development of new therapies and patient management. Since BCL2, an antiapoptotic oncoprotein, is a favourable prognostic factor in breast cancer, we investigated to determine the significance of BCL2 in MPM. Materials and Methods Forty two archival patient tumour sections embedded in paraffin blocks were sectioned and subjected to immunohistochemistry to detect BCL2. The staining intensity and abundance was classified using standard procedures and classified into two groups (0-4 = low & 5-8 = high expression). The distribution of BCL2 groups was examined in the different clinicopathological categories to determine prognosis using Kaplan–Meier survival analysis. Results: Univariate analysis revealed that in almost all clinicopathological categories, high BCL2 expression predisposed patients to a favourable prognosis. Independent of BCL2 expression, univariate analysis also showed that male gender, sarcomatoid histology, high PCI and age at diagnosis ≥ 60 years were associated poor prognosis. Multivariate analysis indicated that for all tumours, males and females, high BCL2 expression was associated with good prognosis. Further, independent of BCL2, age ≥ 60 years is an unfavourable prognostic factor. Conclusion: Expression of BCL2 may serve to distinguish prognosis within the individual clinicopathological categories. BCL2 is also an independent variable in all tumours, males and females, with high expression being associated with good prognosis.     

Does the degree of cell lesion in breast cancer after inductive chemotherapy have any prognostic value?

During 1991 and 1992, 77 patients with breast cancer were treated with induction chemotherapy using the CMFV and FAC protocols at the Lublin Oncological Centre. The degree of cancer cell damage in the specimens obtained postoperatively was evaluated by microscopy. Complete or substantial damage of neoplastic cells was found in 29% of the cases; whereas minimal to no damage was found in 71% of specimens. After assessing the 5-year survival periods of our patients in relation to the degree of cancer cell damage after induction chemotherapy, a statistically significant correlation was noted. Five-year survival without cancer symptoms was observed in 64% of cases in which the cell damage was estimated as considerable, and only in 34% in which the damage was slight or not notable. A much weaker correlation was observed between the degree of breast cancer cell damage after inductive chemotherapy and clinical response.     

Does immunointensity account for the differences in prognostic significance of Bcl-2 expression in non-small cell lung cancer?

Bcl-2 is an oncogenic protein that plays a central role in apoptosis. The association of Bcl-2 expression and prognosis in non-small cell lung cancer (NSCLC) is unclear, with some studies showing improved outcome whilst others show no survival advantage. We evaluated 178 surgically resected NSCLC specimens for Bcl-2 and p53 immunoexpression. Bcl-2 staining was present in 34.9% of cases (weakly staining 24.2%, strongly staining 10.7%), nuclear p53 in 43. 3% and cytoplasmic p53 in 10.7%. There was no association between p53 and survival. Bcl-2 immunoexpression correlated with improved outcome (p=0.04). A sub-group of strongly Bcl-2 staining cases had a poor survival compared to those that stained weakly (p=0.01). The strongly staining cases had a similar survival to negative cases. Immunointensity may therefore account for the disparity in results regarding the prognostic significance of Bcl-2 demonstrated in previous studies.     

Does the number of lymph nodes examined in patients with lymph node-negative breast carcinoma have prognostic significance?

BACKGROUND: There are conflicting data on the prognostic significance of the number of lymph nodes examined in patients with lymph node-negative breast carcinoma. Therefore, the authors analyzed the impact of the number of tumor-free axillary lymph nodes on disease-free survival (DFS) in two distinct patient populations. METHODS: Eight hundred thirty-three consecutive patients with breast carcinoma who underwent mastectomy between 1927 and 1987 and 1094 consecutive patients with breast carcinoma who underwent with breast-conservation therapy between 1984 and 2001 were diagnosed pathologically with negative axillary lymph node status. Patients were stratified into 4 groups according to the number of lymph nodes examined: Group 1 had 1-3 lymph nodes examined, Group 2 had 4-9 lymph nodes examined, Group 3 had 10-20 lymph nodes examined, and Group 4 had >20 lymph nodes examined. RESULTS: In the mastectomy cohort, with a median follow-up of 153 months, the 10-year DFS rate was 70%, 65%, 79%, and 81% for Groups 1-4, respectively. On multivariate analysis, pathologic tumor size (P<0.001) and the number of lymph nodes examined (P=0.010) were significant predictors for long-term DFS. In the breast-conservation cohort, with a median follow-up of 53 months, the 5-year DFS rate was 90%, 91%, 92%, and 95% for Groups 1-4, respectively. On multivariate analysis, the only predictors of DFS were method of detection (clinically vs. mammographically) (P=0.003) and tumor size (P=0.035). CONCLUSIONS: The recovery of <10 lymph nodes in lymph node-negative patients who underwent mastectomy resulted in a 10-15% decreased long-term DFS rate compared with patients who had a more extensive axillary assessment. However, the number of lymph nodes examined did not have an impact on the DFS rate in a contemporary cohort of patients who underwent breast-conservation therapy, which included radiation.     

Does routine grading of invasive lobular cancer of the breast have the same prognostic significance as for ductal cancers?

AIM: The routine tumour grading of invasive ductal carcinoma of the breast has been shown to be a robust determinant of outcome but pathologists have been reluctant to grade lobular cancers. The aim of this study was to determine the prognostic significance of the routine reporting of lobular grade. METHODS: All patients with invasive lobular carcinoma (ILC) treated between 1981 and 1996 were reviewed. Patients with ILC which had been graded were included in the study. These cases were matched with two control patients with invasive ductal carcinoma (IDC) who were operated on in the same year and were closest to the patients in age. Recurrence-free survival was compared with grade for ILC cases and IDC controls using life-table analysis. Similar comparisons were made with the Nottingham Prognostic Index (NPI) between the different prognostic groups. RESULTS: Of 139 cases with ILC, 33 were excluded from the study because 24 were ungraded, five had advanced disease and four had mixed tumours. The mean length of follow-up for ILC cases was 75 months vs 70 months for IDC controls. Recurrence rates for grade I were 10% ILC vs 24% IDC, for grade II 32%vs 32% and for grade III 33%vs 49%. The reported grades for ILC and IDC both showed the expected trend for an increased recurrence rate with more severe tumour grade, but this was only significant for IDC grade II vs grade III (P<0.02) on life-table analysis; only 6% of lobular cancers were reported as grade III. However, there was significant separation of the survival curves when NPI was compared for both lobular and ductal cancers. CONCLUSION: The routine reporting of tumour grade for ILC did not show significant difference in outcome between grade I and grade II, and very few tumours were rated grade III. The validity of grading lobular cancer of the breast requires further evaluation.     

Does p53 codon 72 polymorphism have a prognostic value in carcinoma of the vulva and vagina?

Medical Oncology - Human papilloma virus (HPV) is considered to be responsible for a large part of vaginal and vulvar carcinomas, and the p53 codon 72 polymorphism has been implicated in...     

C-myc protein expression in B-cell acute lymphoblastic leukemia,prognostic significance?

C-myc protein expression has been studied in mature B-cell lymphomas and overexpression has been associated with poor prognosis. We sought to determine the prognostic significance of c-myc protein expression in B-ALL. We found ≥20% c-myc expression to predict risk of persistent disease in all age groups (odds ratio 7.487, p = 0.013). There was no statistically significant association between c-myc expression and risk of relapse or death in our study. Routine c-myc immunostaining may help identify higher risk patients and guide management of B-ALL. Additional studies are needed to further determine the molecular mechanisms and role of c-myc expression in B-ALL.     

Prognostic significance of epithelial/stromal caveolin‐1 expression in prostatic hyperplasia,high grade prostatic intraepithelial hyperplasia and prostatic carcinoma and its correlation with microvessel density

Caveolin-1 may play a role in cancer development and progression. The aim was to record the expression and localization of caveolin-1 in benign prostatic hyperplasia (BPH), high grade prostatic intraepithelial neoplasia (HGPIN) and prostatic carcinoma (PCa). Microvessel density was evaluated with CD34 immunostain. Correlations with known prognostic factors of PCa were recorded. Immunohistochemical expression of caveolin-1 and the MVD was evaluated in 65 cases; BPH (25), HGPIN (20) and PCa (20). Stromal caveolin-1expression was significantly higher in BPH than HGPIN and PCca. There was significant inverse relation between stromal caveolin-1 expression and extension to lymph node and seminal vesicle in carcinoma cases. Epithelial caveolin-1 was significantly higher in carcinomas than in BPH and HGPIN. Epithelial expression in carcinoma was significantly associated with preoperative PSA, Gleason score and lymph node extension. MVD was significantly higher in PCa than in BPH and HGPIN. There were significant relations between MVD and preoperative PSA, Gleason score, lymph node and seminal vesicle extension. Stromal caveolin-1 was associated with low MVD while epithelial caveolin-1 with high MVD. Conclusions: Caveolin-1 plays an important role in prostatic carcinogenesis and metastasis. Stromal expression of caveolin-1 in PCa is lowered in relation to BPH and HGPIN. In PCa; stromal caveolin-1 was associated with good prognostic parameters. Epithelial caveolin-1 is significantly increased in PCa than BPH and HGPIN. It is associated with clinically aggressive disease. Caveolin-1 may play a role in angiogenesis.     

PTEN’s regulation of VEGF and VEGFR1 expression and its clinical significance in myeloid leukemia

Phosphatase and tensin homolog (PTEN) acts as a novel tumor suppressor gene. PTEN protein plays an important role in regulating proliferation, apoptosis, invasion, and migration of many cancer cells. PTEN also modulates angiogenesis mediated by vascular endothelial growth factor (VEGF) via down-regulating PI3K/Akt pathway in many solid tumors. However, the effects of PTEN on VEGF and VEGFR1 (FLT1)-mediated angiogenesis, migration, invasion of leukemia cells, and its clinical significance are still unknown in myeloid leukemia. Therefore, we investigated the effect of PTEN on PI3K/Akt and VEGF/FLT1 pathways by transfecting wild-type PTEN gene to induce high expression of wild-type PTEN gene and protein in chronic myelogenous leukemia cell line K562 cells. We also observed the correlation between the expression levels of PTEN and VEGF/FLT1 and its clinical significance in myeloid leukemia patients. We found that the expression reconstitution of wild-type PTEN had significant effect on inhibiting proliferation, migration, and invasion abilities of K562 cells via down-regulation of Akt phosphorylation and inhibition of VEGF/FLT1 expression. In myeloid leukemia patients, a negative correlation was found between the expression level of PTEN mRNA and that of VEGF and FLT1 mRNA. Down-regulation of PTEN expression accompanied by up-regulation of VEGF and FLT1 mRNA indicated a higher tendency of extramedullary disease in acute myeloid leukemia patients. In conclusion, PTEN could modulate the function of VEGF/VEGFR signaling pathway down-regulation of Akt phosphorylation and that PTEN would be a candidate target to be addressed for inhibiting angiogenesis along with the treatment of myeloid leukemia.     

Pathological and prognostic significance of hypoxia-inducible factor 1α expression in epithelial ovarian cancer: a meta-analysis

Hypoxia-inducible factor-1α (HIF-1α) plays an important role in tumour progression and metastasis. However, the association between HIF-1α and clinicopathological characteristics of epithelial ovarian cancers is controversial. We searched articles on the association between HIF-1α expression and clinicopathological variables of epithelial ovarian cancer in Cochrane Library, Pubmed, Web of Knowledge and China National Knowledge Infrastructure (CNKI) from inception to February 2014. Twenty-five studies were included in the final review. The expression of HIF-1α in cancer or borderline tissue was significantly higher than that in benign tissue (cancer vs. benign, odds ratio (OR) = 9.73 (95 % confidence interval (CI), 4.90, 19.32); P?P?P?=?0.04). The expression of HIF-1α in stages III–IV or lymph node metastasis was significantly higher than that in stages I–II or that without lymph node metastasis, respectively (OR?=?3.01 (95 % CI, 1.92–4.74); P?P?=?0.0004). HIF-1α was associated with histological grade of cancer (grades 3 vs. 1, OR?=?4.52 (95 % CI, 2.79–7.31); P?P?=?0.003; grades 3 vs. 1, OR?=?2.43 (95 % CI), 1.65–3.59; P?P?P?=?0.94; OR?=?1.06 (95 % CI, 0.73–1.55); P?=?0.75). In conclusion, HIF-1α is related to the malignant degree, FIGO stage, histological grade, lymph node metastasis and 5-year survival rate of epithelial ovarian cancer. It may play an important role in clinical treatment and prognostic evaluation.     

The methodology of quantitation of microvessel density and prognostic value of neovascularization associated with long‐term survival in Japanese patients with breast cancer

The present study updates results on methodology of quantitation of tumor neovascularization and those on the prognostic value of microvessel density (MVD) in breast cancer tissue previously published in the World J. Surg. 21: 49–56, 1997. The followup period of observation of the series was extended to 20 years, and new biological indicators (i.e., proliferating cell nuclear antigen (PCNA), cerbB2, and p53) were included in the analysis. There were 109 patients with primary breast cancer, from 1971 to 1979, followed up for a median of 14 years (range, 1–20). A representative median longitudinal section of each breast tumor was immunohistochemically stained with factor VIIIrelated antigen and analyzed. The three methods of identifying MVD were: (1) average microvessel count (AMC)/mm2, (2) central microvessel count (CMC)/mm2, and (3) highest microvessel count (HMC)/mm2. Thirtyone patients (28.4%) died of breast cancer. There was a relationship between MVD and peritumor blood vessel invasion (AMC: p = 0.0114, CMC: p = 0.0319, and HMC: p = 0.0009). However, there was no relationship between MVD and other factors. Univariate analysis showed that node status (p < 0.0001), histological grade (p < 0.0001), clinical tumor size (T) (p = 0.0002), PCNA (p = 0.0033), p53 (p = 0.0043), mitotic grade (p = 0.0092), AMC (p = 0.0214), and peritumor lymphatic vessel invasion (p = 0.0467) were significantly predictive of overall survival. HMC was borderline significant (p = 0.0702), while CMC and cerbB2 were not significant. Multivariate analysis showed that T (p = 0.0005), node status (p = 0.0053), and AMC (p = 0.0485) were independent factors, but neither CMC nor HMC was independent. AMC, a significant independent prognostic factor, might be a better method than the others for evaluating angiogenesis, but further and larger studies are warranted.     

Does histologic grade have a role in the management of head and neck cancers?

PURPOSE: High histologic grade is usually associated with a greater propensity to distant metastases (DM). Its role to predict DM in head and neck cancer is not yet defined. The aim of this study is to evaluate the role of histologic grade as an independent predictor of DM and to determine a subgroup of patients who may benefit from systemic chemotherapy. PATIENTS AND METHODS: This is a retrospective study of 1,266 consecutive patients treated by definitive or postoperative radiotherapy between 1989 and 1997. All patients received at least 50 Gy. All stages and subsites of head/neck were included. DM rates were evaluated by the Kaplan-Meier method with a subsequent Cox analysis. RESULTS: There is a strong correlation of grade with N stage (P <.000001). The metastases-free survival (MFS) was 98%, 90%, and 72% for grades 1, 2, and 3, respectively (P <.000001). In patients with N0 stage, MFS is always greater than 90%, whatever the grade. In the 222 N1 patients, MFS was more than 90% in grade 1 and 2 but dropped to 75% for grade 3 (P =.001). In patients with N2 and N3, MFS was 91%, 79%, and 59% for grades 1, 2, and 3, respectively (P =.008). The same conclusion is applicable when only patients with neck control are analyzed. In a Cox model, grade was an independent predictor of DM (P =.000001) as well as T stage (P =.003), N stage (P =.000001), and neck failure (P =.0003). Higher grade was also an independent predictor of survival (P =.02). CONCLUSION: Patients with histologic grade 1 and grade 2 (except N3) are at low risk of DM. Patients with grade 2 and N3 or patients with grade 3 and N1 to N3 have a higher risk of distant metastases and should be considered for systemic treatment.     

Does tamoxifen change oestrogen and progesterone receptor expression in the endometrium and breast?

We studied the expression of oestrogen and progesterone receptors (ER, PR) in postmenopausal women receiving tamoxifen for breast cancer. In addition the literature addressing the question of ER and PR expression in breast tissue during treatment with tamoxifen was reviewed. We demonstrated consistent expression of ER and PR in endometria from patients receiving tamoxifen, with a trend towards a higher proportion of receptor positive specimens during tamoxifen. In breast cancer tissue, the ER content seemed to be reduced following tamoxifen treatment. After short time exposure to tamoxifen, the PR appeared to be increased, longer treatment caused the PR to go down to pretreatment levels or below.     

Could the determination of Aspergillus fumigatus mating type have prognostic value in invasive aspergillosis?

A clear link between mating type and virulence has been demonstrated for some fungal pathogens, but not for Aspergillus fumigatus as of yet. An association between mating type and invasiveness has recently been established. The mating type proportion (MAT1‐1:MAT1‐2) of 213 A. fumigatus strains was determined (48.5%:51.5%) and results were in agreement with previous studies. However, these percentages changed when the strain collection was divided into azole‐susceptible and ‐resistant strains. The 163 susceptible strains kept these proportions, but among the 50 azole‐resistant strains 60.0% MAT1‐1 and 40% MAT1‐2 were found. Moreover, looking at the clinical outcome associated to 27 azole‐resistant strains, we found that MAT1‐1 was linked to a high mortality rate (64%), whereas the rate associated to MAT1‐2 genotype was markedly lower (15%). The pathogenicity linked to the Mat type was tested in a Galleria mellonella model of infection, showing that MAT1‐1 strains were consistently more pathogenic than MAT1‐2, independently of their susceptibility phenotype. This data would suggest that A. fumigatus mating type determination at the time of diagnosis could have a prognostic value in invasive aspergillosis.     

Semaphorin,neuropilin and VEGF expression in glial tumours: SEMA3G,a prognostic marker?

Gliomas are characterised by local infiltration, migration of tumour cells across long distances and sustained angiogenesis; therefore, proteins involved in these processes are most likely important. Such candidates are semaphorins involved in axon guidance and cell migration. In addition, semaphorins regulate tumour progression and angiogenesis. For cell signalling, class-4 semaphorins bind directly to plexins, whereas class-3 semaphorins require additional neuropilin (NRP) receptors that also bind VEGF(165). The anti-angiogenic activity of class-3 semaphorins can be explained by competition with VEGF(165) for NRP binding. In this study, we analysed the expressions of seven semaphorins of class-3, SEMA4D, VEGF and the NRP1 and NRP2 receptors in 38 adult glial tumours. In these tumours, SEMA3B, SEMA3G and NRP2 expressions were related to prolonged survival. In addition, SEMA3D expression was reduced in high-grade as compared with low-grade gliomas. In contrast, VEGF correlated with higher grade and poor survival. Thus, our data suggest a function for a subset of class-3 semaphorins as inhibitors of tumour progression, and the prognostic value of the VEGF/SEMA3 balance in adult gliomas. Moreover, in multivariate analysis, SEMA3G was found to be the only significant prognostic marker.