Journal of Carcinogenesis最新文献

Introduction: Breast cancer is the most frequently diagnosed cancer among women in India; however, there are no studies addressing long-term survival (10 years and above). This study sought to evaluate long-term oncological outcome among women with breast cancer treated with a curative intent.

Materials and methods: This is a retrospective cohort analysis of 1301 breast cancer patients of all stages who had received primary treatment with curative intent from 2004 to 2010 at a single cancer institution of India.

Results: A total of 1301 breast cancer patients were available for final analysis. The median age was 51 years (range, 21-86 years). 70.25% of the patients had early breast cancer (EBC), 21.9% had locally advanced breast cancer, and 7.85% of the patients with de novo metastatic disease also underwent surgery. 56.5% of the patients had hormone-sensitive tumors, human epidermal growth factor receptor 2 over expression was seen in 17%, and triple-negative tumors accounted for 26.2% of the patients. The 5- and 10-year overall survival (OS) of the entire cohort was 79% and 66%, and the 5- and 10-year breast cancer-specific survival (BCSS) was 79% and 70%, respectively. OS and BCSS were 51% and 58%, respectively, at 15-year follow-up after primary cancer treatment. On multivariate analysis, the factors associated with prolonged survival were age ≤50 years, EBC, and treatment during the later period (2008-2010).

Conclusion: Difference between OS and BCSS was found to have an increasing trend during 10-15-year follow-up, the difference being 4% at 10 years and 7% at 15 years. Age ≤50 years, early-stage disease at presentation, and primary cancer treatment in later years (2008-2010) were favorable predictors for 10-year survival.

Background: Filamin A is an actin-crosslinking protein expressed in many malignancies, although its prognostic and therapeutic role in breast cancer is not studied. There is enigma regarding its dual role in cancer, the tumor-progressing or tumor-suppressing effects depending on the site to which it localizes in the cell. The current study aimed to detect Filamin A expression in breast cancer and its association with other biomarkers and other clinicopathological parameters and established risk factors in breast cancer so that it can be a potential site for targeted therapy.

Materials and methods: One hundred female patients of histologically proven breast cancer who presented to our hospital over a 2-year period were included in the study. None of the patients received prior radiotherapy, chemotherapy, or immunotherapy. Patients with recurrent breast cancer are not included in the study. All study cases are subjected to immunohistochemistry for estrogen receptor, progesterone receptor, Her2 neu, and ki-67 from core biopsy tissue of cases diagnosed as breast carcinoma. Tissue sections were subjected to immunohistochemistry with anti-Filamin A.

Results: Filamin A is expressed in 69% of cases of invasive breast cancer in our study. There was no statistically significant relationship of Filamin A immunoexpression with histological grade, age, parity, oral contraceptive use, smokeless tobacco use, TNM staging, clinical staging, clinical prognostic staging, and also ER, PR, Her2 neu, and ki-67 status (P > 0.05). Thus, it appears to be an independent biomarker in breast carcinoma. Filamin A was expressed only in the cytoplasm in all our study cases. Filamin A expression can be observed in adjacent normal breast tissue and benign fibroadenoma tissues also, but the pattern of expression is mainly membranous with cytoplasmic positivity. The cytoplasmic expression is seen in malignant cells as well as normal breast and benign tumor sections implicating the dual role of Filamin A in breast cancer.

Conclusion: No significant correlation could be found between Filamin A expression and clinicopathological parameters in our study. The cytoplasmic expression is seen in malignant cells as well as normal breast and benign tumor sections implicating the dual role of Filamin A in breast cancer. Filamin A immunoexpression should be further correlated with metastasis-free survival period of breast cancer patients.

Background: Spalt-like transcription factor 4 (SALL4) is a stem cell marker that plays a critical role in maintaining the pluripotency and self-renewal of embryonic and hematopoietic stem cells. Only a few studies have been done to apprehend the expression of SALL4 in the potentially malignant oral lesion (leukoplakia with dysplasia) and oral squamous cell carcinoma (OSCC).

Aim: The aim of this study is to evaluate the expression of SALL4 in leukoplakia with dysplasia and OSCC and to correlate the expression of the marker (SALL4) with the various clinicopathological parameters and patient outcome.

Materials and methods: Immunohistochemistry for SALL4 protein was performed on 140 cases: those histopathologically confirmed cases of leukoplakia with dysplasia (n = 30) and OSCC (n = 110). Ten cases of nonepithelial neoplasm (fibroepithelial hyperplasia and excised tissue surrounding impacted third molars) were taken as control. Statistical analyses were applied to evaluate correlations between SALL4 overexpression and clinicopathological features of leukoplakia and OSCC. Survival rates were analyzed using Kaplan-Meier method.

Results: SALL4 positivity was observed to be higher (P = 0.001) in the tumor cells of OSCC with Immuno Reactive Score (IRS) ranging from 0 to 9. Poorly differentiated squamous cell carcinoma (SCC) had paramount higher expression with a median IRS of 6. Similar IRS and above (IRS, 6-9) was observed in Stage I (five cases), which recurred and well-differentiated cases with metastasis (four cases) while in leukoplakia with dysplasia the SALL4 expression was weak with a range of 2-4.

Conclusions: SALL4 being one of the cancer stem cell molecules plays an important role in the progression of oral cancer, which was evident in this study. This could also account for aggressive clinical behavior. Follow-up of these patients would relate this molecule could be responsible for cancer relapse. Patients diagnosed to have oral epithelial dysplasia had a low expression of SALL4, are under follow-up, although seven cases did transform to SCC. Thus, we conclude, SALL4 may be of prognostic relevance, but in oral epithelial dysplasia, it requires further investigations.

Introduction: Lung cancer (LC), among all other cancers, is the leading cause of death worldwide, while the third most common cancer-causing mortality in India. Several techniques of the assay for early detection of cancer that improve survival rates have been employed in tissues and cell lines. Reverse transcriptase quantitative polymerase chain reaction (RTqPCR) is one of the most common techniques employed for gene expression studies for the normalization of a target gene using a reference gene (RG). The present study used the three most common RGs: glyceraldehyde-3-phosphate dehydrogenase (GAPDH), β-Actin, and 18s ribosomal ribonucleic acid (18s rRNA), which were assessed by qPCR to validate, as of which is a more effective RG in blood samples of LC patients.

Materials and methods: A total of thirty participants with LC of non-small cell and small cell type were included along with twenty healthy controls. Ribonucleic acid (RNA) isolated from peripheral blood mononuclear cells was quantified, prepared for complementary deoxyribose nucleic acid synthesis, and analyzed for expression of three RG on RTqPCR.

Results: Expression levels as Ct values of studied RG were reported as mean ± standard deviation for GAPDH (26.97 ± 5.107), β-actin (20.5 ± 2.3), and 18s rRNA (25.10 ± 4.075). GAPDH showed the lowest expression, whereas β-actin showed the highest expression among the studied RG in subjects of LC. The expression of GAPDH and 18s rRNA were statistically significantly lower than β-actin (p < 0.0001), whereas expression levels of GAPDH and 18s rRNA were comparable. However, the expression level of only β-actin in LC patients was comparable with healthy controls with P < 0.1611 at 95% confidence interval.

Conclusion: It is concluded that β -actin may be considered the most suitable RG isolated and studied from peripheral blood mononuclear cells using RT qPCR in LC.

[This corrects the article on p. 2 in vol. 19, PMID: 32684850.].

Context: Lung cancer is the leading cause of cancer-related deaths worldwide. The constitutive activation of multiple signaling pathways is the major cause of carcinogenesis.

Aims: The study evaluates the frequency of Kirsten rat sarcoma virus (KRAS) protein overexpression and correlates with clinicopathological and histomorphological features in non-small cell lung carcinoma (NSCLC)-adenocarcinoma.

Settings and design: Tertiary hospital-based retrospective and prospective case series included 100 cases of NSCLC-adenocarcinoma.

Materials and methods: The basic panel of Immunohistochemistry including Napsin-A, thyroid transcription factor-1 (TTF-1), and markers for squamous differentiation, p-40 was used in formalin-fixed paraffin-embedded tissue blocks. The KRAS monoclonal antibody (9.13, Thermo Fisher Scientific, USA) was used.

Statistical analysis used: The IBM-Statistical Package for the Social Sciences (SPSS) (SPSS, International Business Machines Corporation, New York, NY, USA) analysis software, version 16 was used for all statistical calculations.

Results: KRAS protein expressed in 28.0% (28/100) cases. Cases were grouped as KRAS positive and negative. TTF-1 and Napsin-A were expressed in 89.25% (n = 25) and 92.86% (n = 26) cases, respectively. Stage IV clinical disease was identified in 55% of cases, and 36.84% of cases had a mean survival between 6 and 12 months. In KRAS positive group, the most common pattern of cellular arrangement was acinar/loose clusters pattern present in 64.29% (n = 21) and 75.0% (n = 18) cases followed by the solid pattern present in 42.86% of cases (n = 12), respectively. Necrosis was identified in 57.14% (n = 16) cases. Mucin pattern was present in 32.14% of cases (n = 9), which was significantly different when compared with the KRAS negative group (P = 0.036).

Conclusions: This finding may imply that KRAS mutations may not be entirely triggered by alterations induced by carcinogens in smoke. KRAS gene is frequently mutated in pulmonary tumors. It should be tested in NSCLC owing to its predictive and prognostic effects.

Context: Controversies prevail regarding the true predictive role of epithelial-mesenchymal transition (EMT) biomarkers in metastasis of oral squamous cell carcinoma (OSCC). There is also limited research carried on till date wherein the protein and gene expression of EMT biomarkers have been investigated simultaneously in the Indian population.

Aim: The aim of this study was to assess the gene expression and quantitative protein expression of EMT biomarkers using conventional method and MATLAB software and to determine if there is any difference in the expression between metastatic and nonmetastatic OSCCs with clinicopathologic correlation.

Settings and design: Twenty metastatic and nonmetastatic OSCC tissue sections each were obtained from department archives. Gene expression and quantified protein expression of EMT markers were done and correlated with clinical parameters.

Subjects and methods: Sections immunostained for EMT biomarkers were evaluated using semi-quantitative and quantitative (MATLAB) methods. Gene expression using semi-quantitative reverse transcriptase-polymerase chain reaction was done. These findings were correlated with clinical parameters.

Statistical analysis used: Pearson's Chi-square test, Student's t-test, and univariate logistic regression analysis were performed using SPSS software.

Results: The low immunoexpression of E-cadherin and β-catenin and the high expression of matrix metalloproteinase (MMP)-2 and MMP-9 correlate with Stages III and IV showing high metastatic risk. Furthermore, the upregulated MMP-2 and MMP-9 gene expressions in advanced clinical stages of OSCC have high metastatic potential.

Conclusions: This study is the first of its kind to employ texture and color segmentation in MATLAB to objectively assess the protein expression of EMT biomarkers. This research is instrumental in studying the protein and gene expressions of EMT markers with clinical correlation.

Introduction: The behavior of the laryngeal squamous cell carcinoma (LSCC) is marked by the degree of cell proliferation and differentiation. Ki-67 is regarded as a promising proliferation marker and has been correlated as a prognostic indicator.

Aim: The aim of the present study is to determine the Ki-67 expression and its prognostic value in LSCC.

Materials and methods: A total of eighty patients with early glottic carcinoma stage (Tis, T₁, T₂) N₀ M₀ were included. After preoperative workup, surgery was performed using LUMINES 40C CO₂ laser and tumor resection was done which was sent for histopathological diagnosis and immunohistochemistry (IHC). IHC for Ki-67 expression could be done only on 65 specimens.

Results: All patients had microscopically confirmed squamous cell carcinoma. Forty-eight out of 65 specimens (75%) stained positive for Ki-67 and 17 (25%) stained negative. Out of total 48, 29 stained 2+, 11 stained 3+ and 8 stained 4+. No difference was found in Ki-67 expression in relation to age, sex, T stage, and histological grading. The association of Ki-67 with recurrence was found to be statistically significant. The association of Ki-67 with survival was also studied and Ki-67 positivity is associated with increased mortality rate, although it was not statistically significant.

Conclusion: The proliferative index as measured by immunohistochemical staining of Ki-67 correlates with the tumor aggressiveness. High Ki-67 index is associated with early relapse and poor survival outcomes.

Introduction: Radiation is an important tool in the diagnostic and curative treatment of many cancers. Ionizing radiation induces many biochemical changes in the cells. The present study was designed to estimate the level of neurotransmitters in the distinct brain tissue of Swiss albino mice before exposing gamma radiation.

Materials and methods: The mice were treated with 0.25 and 1 g/kg body weight of Cynodon dactylon extract (CDE) via oral gavage for 7 days and subjected to 5 Gy of gamma radiation. The estimation of monoamines was performed in the cortex and cerebellum separately.

Results: Mice exposed to a sublethal dose 5 Gy of gamma radiation causes a significant decrease in dopamine, norepinephrine, epinephrine, and serotonin levels compared to normal. The mice treated with 0.25 and 1 g/kg body weight of CDE via oral gavage for 7 days showed significant improvement in the level of monoamine neurotransmitters in both the cortex and cerebellum homogenate.

Conclusion: Oral administration of antioxidant-rich C. dactylon has shown a neuromodulatory effect against radiation-induced depletion of neurotransmitters in the brain tissues.

Introduction: Gall bladder cancer (GBC) tends to present in advanced stages, therefore, early diagnosis of GBC is necessary. There is no ideal single tumor marker available presently for the diagnosis and prognosis of GBC. Platelet distribution width (PDW) is an early marker for activated platelets and has been used in a variety of tumors to assess prognosis. This study was designed to evaluate the utility of PDW in identifying GBC patients and its association with tumor markers, staging and resectability of GBC.

Materials and methods: This cross sectional study was done on 100 patients of GBC and 100 age- and sex- matched healthy controls. PDW was evaluated and compared between GBC and healthy controls. Receiver-operating characteristics was plotted to determine optimal cut-off for identifying GBC patients and to determine sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of PDW. Correlation between serum tumor markers (carbohydrate antigen 19-9, carcinoembryonic antigen, and carbohydrate antigen 125) and PDW were evaluated. Association of PDW with hyperbilirubinemia, staging and resectability of GBC was also studied.

Results: A significantly higher PDW with a median of 18.1 was observed in GBC as compared to healthy controls with median value of 13. PDW was found to have a very high sensitivity (90%), specificity (95%), PPV (94%) and NPV (90%) in identifying GBC at cut-off of 16 with area under the curve (AUC) of 0.97. An increase of PDW was observed with increasing stage and unresectable GBC. However, it was not statistically significant. Significant positive correlation was observed between PDW and all three serum tumor markers and good positive correlation with r = 0.61 was observed with CA 19-9.

Conclusion: PDW was associated with GBC and may be considered as a cost- effective marker in adjunct to other investigations for the diagnosis of GBC.