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Asian Pacific Journal of Cancer... Jun 2024The alterations of EGFR and HER2/neu as growth factor receptors and the cytoplasmic signal transduction proteins of RAS/RAF/MAP kinases including its end effector...
Evaluation of the Expression EGFR, HER2/NEU and the End Effector ERK of the RAS/RAF/MAP Kinase Pathway in Prostatic Adenocarcinoma for a Possible Role as New Target Therapy.
UNLABELLED
The alterations of EGFR and HER2/neu as growth factor receptors and the cytoplasmic signal transduction proteins of RAS/RAF/MAP kinases including its end effector molecule (ERK) are important in the carcinogenesis of many tumors. The activation of these protooncogenes in prostate cancer is still under investigation. The aim of this work was to study EGFR, HER2- neu, inactive (non-phosphorylated) and active (phosphorylated) ERK expression in prostatic adenocarcinomas in correlation to the clinical and pathological parameters.
METHODS
Immunohistochemistry- using tissue microarrays- for EGFR, HER2/neu, non-phosphorylated, and phosphor-ERK, was performed on tissues from 166 patients- with primary prostatic adenocarcinoma with no prior treatment-. The results of different markers expression were correlated with the clinical and pathological parameters and were analyzed statistically.
RESULTS
The prostatic tissue showed EGFR, HER2 neu, phosphorylated and non-phosphorylated ERK expression in 8.4%, 1.4%, 78.2%, and 83.4% respectively whether low (patchy) or high expression (diffuse). There were no significant correlations found between patient characteristics and expression of the tested markers. The negative immune reactivity for non-phosphorylated ERK and EGFR- was significantly correlated with high tumor stage (p values 0.03 and 0.01, respectively).
CONCLUSION
EGFR and HER2/neu may play a limited role in prostatic adenocarcinoma as they showed positive expression in a limited number of the examined tissues specifically HER2neu. The expression of non-phosphorylated ERK (mostly weak to moderate) and phosphorylated ERK (mostly moderate to strong)- was appreciated in most cases. Thus, we suggest that anti-EGFR drugs may have a limited role in the treatment of castrate-resistant prostate cancer, but anti-MEK/ERK drugs may have more promising role as a target therapy. It is recommended to perform further molecular testing to elucidate the exact mechanism and significance of these markers.
Topics: Humans; Male; Prostatic Neoplasms; ErbB Receptors; Receptor, ErbB-2; Adenocarcinoma; Biomarkers, Tumor; Aged; Middle Aged; Prognosis; Phosphorylation; raf Kinases; Follow-Up Studies; MAP Kinase Signaling System; ras Proteins; Aged, 80 and over; Extracellular Signal-Regulated MAP Kinases; Signal Transduction
PubMed: 38918683
DOI: 10.31557/APJCP.2024.25.6.2193 -
Asian Pacific Journal of Cancer... Jun 2024Standard tools are not sensitive enough for hepatocellular carcinoma (HCC) early detection. This study aimed to evaluate the accuracy of dickkopf-1 (DKK1) and soluble...
BACKGROUND
Standard tools are not sensitive enough for hepatocellular carcinoma (HCC) early detection. This study aimed to evaluate the accuracy of dickkopf-1 (DKK1) and soluble Axl (sAxl) and their combined for early differentiating of HCC from premalignant benign liver diseases.
METHODS
A total of 210 chronic hepatitis C (CHC) patients (55 fibrotic, 45 cirrhotic and 110 HCC) were enrolled. Both DKK1 and sAxl were tested using ELISA for all participants.
RESULTS
HCC patients were accompanied by a significant increase (P<0.05) in DKK1 (5.38±2.05 ng/mL) and sAxl (178.02±49.39 ng/mL) compared to patients with fibrosis (2.16±0.6, 97.63±19.71 ng/mL, respectively) and cirrhosis (2.62±0.8, 121.84±34.66 ng/mL, respectively). Both DKK1 (AUC=0.852) and sAxl (AUC=0.882) had a good diagnostic accuracy in separating HCC from all non-HCC patients. Multiplying DKK1 with sAXL yielded values that significantly (P=0.0001) increased in patients who developed HCC (674.3 (434.2-1413.9)) versus fibrotic (204.9 (161.7-262)) and cirrhotic (254.4 (205.4-343.7)) patients. This model improves HCC diagnostic performances [AUC=0.921; sensitivity 90.9%, specificity 87%, PPV 88.5%, NPV 89.7% and efficiency 89.1%]. Elevated DKK1×sAxl values were associated with aggressive tumor features including multiple nodules, large size, Child-Pugh and BCLC late stages.
CONCLUSIONS
combined use of DKK1×sAxl is simple and feasible HCC diagnostic model that could enhance HCC diagnostic accuracy and could replace AFP in follow up of patients with premalignant diseases.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Intercellular Signaling Peptides and Proteins; Male; Axl Receptor Tyrosine Kinase; Female; Middle Aged; Receptor Protein-Tyrosine Kinases; Biomarkers, Tumor; Proto-Oncogene Proteins; Hepatitis C, Chronic; Prognosis; Liver Cirrhosis; Follow-Up Studies; Adult; Hepacivirus; Early Detection of Cancer; Aged
PubMed: 38918682
DOI: 10.31557/APJCP.2024.25.6.2185 -
Asian Pacific Journal of Cancer... Jun 2024Mucin-producing cholangiocarcinoma (MPCC) was rare biliary tract malignancy. Studies regarding this type of cholangiocarcinoma (CCA) were limited, particularly the... (Comparative Study)
Comparative Study
BACKGROUND
Mucin-producing cholangiocarcinoma (MPCC) was rare biliary tract malignancy. Studies regarding this type of cholangiocarcinoma (CCA) were limited, particularly the survival outcome. We aim to evaluate the survival rate, median survival time after surgery among CCA patients and to determine the association between MPCC and survival.
OBJECTIVE
To evaluate survival rate, median survival time after surgery among cholangiocarcinoma patients and to determine the association between mucin-producing cholangiocarcinoma and survival.
METHODS
CCA patients who underwent surgery between 2013 and 2020 from the Cholangiocarcinoma Screening and Care Program (CASCAP), Northeast Thailand were included in the study. The MPCC was based on pathological findings after surgery. The survival of CCA patients was verified through medical records and civil registration. Survival rates and median survival time since the date of CCA surgery and its 95% confidence intervals (CI) were estimated. Multiple cox regression was performed to evaluate factors associated with survival which were quantified by adjusted hazard ratios (AHR) and their 95% CI.
RESULTS
Of 1,249 CCA patients which constituted 24,593 person-months, 687 died at the completion of the study. The overall incidence rate was 2.79 per 100 patients per month, the median survival time was 21.77 months (95% CI: 19.87 - 23.84), and the 5-year survival rate was 28.29% (95% CI: 24.99 - 31.67). From these patients, 210 (16.81%) were MPCC, the incidence rate was 1.81 per 100 patients per month, median survival time was 41.21 months (95% CI: 26.16 - 81.97), and 5-year survival rate was 44.69% (95% CI: 32.47 - 56.16). MPCC were 35% less likely to died compared with non-MPCC (AHR = 0.65; 95% CI: 0.50 - 0.84).
CONCLUSIONS
Our study revealed that CCA patients with MPCC had longer survival times and higher survival rates than those without MPCC. This classification will lead to appropriate treatment guidelines for CCA patients.
Topics: Humans; Cholangiocarcinoma; Female; Male; Bile Duct Neoplasms; Middle Aged; Survival Rate; Thailand; Prognosis; Aged; Mucins; Follow-Up Studies
PubMed: 38918677
DOI: 10.31557/APJCP.2024.25.6.2139 -
Asian Pacific Journal of Cancer... Jun 2024The aim of this study was to evaluate the expression profiles of PIWI-like protein- 2 (PIWIL2), and HepPar1 and their immunohistochemical (IHC) characteristics in...
OBJECTIVE
The aim of this study was to evaluate the expression profiles of PIWI-like protein- 2 (PIWIL2), and HepPar1 and their immunohistochemical (IHC) characteristics in Hepatocellular Carcinoma (HCC), and determine their correlation with clinicopathological parameters of this type of cancer to determine their diagnostic value in combination.
METHODS
Seventy-five patients with HCC were assessed for the expression of PIWIL2 in serum and tissue using real-time polymerase chain reaction (RT-PCR) and IHC was performed for PIWIL2 and HepPar1 was performed on all patients.
RESULTS
A statistically significantly higher level of PIWIL2 was found in HCC compared to controls (p≤0.001). Both HepPar1 and PIWIL2 were detected in 84% of HCC cases, the diagnostic and prognostic factors for PIWIL2 were found to be significant in liver tumour tissue samples and non-tumorous sections p<0.001, and the same was observed for serum samples and results of healthy serum controls (p<0.001) when compared to AFP.
CONCLUSION
Our results affirm the hypothesis that reactivation of PIWI expression in various caner types is crucial for cancer development, and that a possible panel maybe used for these markers HCC diagnosis.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Argonaute Proteins; Biomarkers, Tumor; Male; Female; Middle Aged; Prognosis; Case-Control Studies; Follow-Up Studies; Adult; alpha-Fetoproteins; Aged
PubMed: 38918675
DOI: 10.31557/APJCP.2024.25.6.2123 -
Asian Pacific Journal of Cancer... Jun 2024This study examined the morphological changes in the colonic mucosa and the presence of inflammation in rats induced with 1,2-dimethylhydrazine (DMH) 30 mg/kg BW over 9,...
OBJECTIVE
This study examined the morphological changes in the colonic mucosa and the presence of inflammation in rats induced with 1,2-dimethylhydrazine (DMH) 30 mg/kg BW over 9, 11, and 13 weeks without a latency period.
METHODS
Hematoxylin and eosin staining was performed to assess the morphology and characteristic alteration of the epitheliocytes in the colon. Immunohistochemistry was employed to assess the expression of tumor necrosis factor (TNF)-α and cyclooxygenase-2 (COX-2). The difference in the severity of inflammation and COX-2 expression was examined using one-way analysis of variance. The correlation of COX-2 expression with the severity of inflammation was analyzed using Spearman's rank correlation test.
RESULT
Until week 13, chronic inflammation and non-hyperplastic and hyperplastic aberrant crypt foci occurred. The severity of inflammation gradually shifted from high moderate to low moderate. TNF-α expression was high in all groups; however, COX-2 expression was gradually lower with longer duration of induction, which corresponded with the severity of inflammation.
CONCLUSION
DMH induction until week 13 without a latency period caused chronic inflammation without the formation of adenoma or adenocarcinoma. A very strong correlation was established between COX-2 expression and inflammation.
Topics: Animals; 1,2-Dimethylhydrazine; Rats; Colorectal Neoplasms; Cyclooxygenase 2; Inflammation; Male; Tumor Necrosis Factor-alpha; Intestinal Mucosa; Carcinogens; Rats, Sprague-Dawley; Aberrant Crypt Foci; Colon; Adenocarcinoma
PubMed: 38918668
DOI: 10.31557/APJCP.2024.25.6.2059 -
Asian Pacific Journal of Cancer... Jun 2024This study was designed to determine the role of BRAF V600E and TERT mutations in the incidence of neck lymph node (LN) metastasis in patients with papillary thyroid...
OBJECTIVE
This study was designed to determine the role of BRAF V600E and TERT mutations in the incidence of neck lymph node (LN) metastasis in patients with papillary thyroid carcinoma (PTC).
METHODS
This was a cross-sectional study, involving PTC patients at Dr. Cipto Mangunkusumo Hospital, Jakarta. Data were obtained retrospectively based on medical records, except for BRAF V600E and TERT promoter mutations. Tumor tissue specimens of PTC's patients were transferred to the Integrated Laboratory of Faculty of Medicine, Universitas Indonesia. BRAF gene multiplication was performed with KOD One PCR Master Mix (Toyobo KMM-201), while TERT gene multiplication was performed with PCR Master Mix. Data analysis was performed with SPSS version 20. The data were analyzed using univariate and bivariate analysis with the Chi-Square test.
RESULT
42 PTC patients were included in the study; 19 (45%) had BRAF mutation, 20 (48%) had TERT mutation, and 20 (48%) had LN metastases. BRAF V600E mutation was associated with LN metastasis [p<0.001, OR = 25.33 (95% CI 4.92 - 130.34)], while TERT mutation was not. Patients with BRAF+ and TERT- mutations were 18.00 times (95% CI 2.01 - 161.05) more likely to develop LN metastasis than patients with BRAF- and TERT-. Furthermore, the presence of TERT mutation along with BRAF mutation increased the risk to 60.00 (95% CI 4.72 - 763.04) higher than patients with BRAF- and TERT-.
CONCLUSION
BRAF mutation was associated with LN metastasis in PTC patients, but not TERT mutations. However, the presence of TERT mutation in PTC's patients with BRAF mutation increased the risk of LN metastasis.
Topics: Humans; Telomerase; Proto-Oncogene Proteins B-raf; Female; Lymphatic Metastasis; Male; Promoter Regions, Genetic; Thyroid Neoplasms; Cross-Sectional Studies; Mutation; Adult; Middle Aged; Retrospective Studies; Thyroid Cancer, Papillary; Prognosis; Follow-Up Studies; Carcinoma, Papillary; Indonesia; Biomarkers, Tumor
PubMed: 38918666
DOI: 10.31557/APJCP.2024.25.6.2043 -
Asian Pacific Journal of Cancer... Jun 2024Iodine intake can affect thyroid and breast cells, and urinary iodine concentration (UIC) is an effective biomarker for iodine intake.
UNLABELLED
Iodine intake can affect thyroid and breast cells, and urinary iodine concentration (UIC) is an effective biomarker for iodine intake.
OBJECTIVES
This study aimed to analyze the correlation between urinary iodine concentration in differentiated thyroid cancer (DTC) and breast cancer (BC) subjects.
METHODS
The study consisted of 80 subjects divided into case (20 DTC and 20 BC subjects) and control (40 subjects). Morning urine or spot urine was used for UIC measurement.
RESULTS
In thyroid cancer, UIC median patients and controls were 195.45 ± 133.61 µg/L and 145 ± 39.64 µg/L, respectively, with p =0.33. The UIC median of PTC subjects was significantly higher compared to FTC subjects, 227.12±130.98 μg/L versus 68.75±22.95 μg/L, p=0.00, and papillary thyroid cancer is closely related to a high iodine excretion in urine with contingency coefficient (c)=0.722. In BC patients, regardless of subtypes, breast cancer subjects showed a significantly lower iodine excretion level. The median of UIC patients and controls were 80.05 ± 38.24 µg/L and 144.25 ± 36.79 µg/L, respectively, p=0.000.
CONCLUSIONS
Iodine urine concentrations strongly correlate with the type of DTC histopathology, and in BC subjects, IUC was significantly lower compared to the control.
Topics: Humans; Female; Iodine; Thyroid Neoplasms; Breast Neoplasms; Case-Control Studies; Middle Aged; Adult; Prognosis; Male; Follow-Up Studies; Carcinoma, Papillary; Adenocarcinoma, Follicular; Thyroid Cancer, Papillary
PubMed: 38918646
DOI: 10.31557/APJCP.2024.25.6.1869 -
International Journal of Surgery Case... Jun 2024Large cell neuroendocrine carcinomas of the colon (LCNECC) are exceptionally rare, comprising only 0.2 % of all colonic carcinomas. Their diagnosis poses a significant...
INTRODUCTION AND IMPORTANCE
Large cell neuroendocrine carcinomas of the colon (LCNECC) are exceptionally rare, comprising only 0.2 % of all colonic carcinomas. Their diagnosis poses a significant challenge due to their propensity to mimic colonic adenocarcinomas. Typically diagnosed at advanced stages, LCNECCs carry a grim prognosis. Herein, we present a rare case of LCNECC and aim to elucidate its clinico-pathological characteristics.
CASE PRESENTATION
A 56-year-old female patient presented with complaints of constipation, abdominal pain, and weight loss. On physical examination, a sizable mass was palpable in the right flank. Colonoscopy revealed a polyp in the descending colon and a friable multinodular stenosing mass in the ascending colon. Microscopic examination of the biopsy from the ascending colon mass exhibited a poorly differentiated large cell carcinomatous proliferation with positivity for synaptophysin and CD56, along with a Ki-67 proliferation index of 50 %. The polyp in the descending colon was consistent with a low-grade dysplastic tubular adenoma. A diagnosis of LCNECC with synchronous low-grade dysplastic tubular adenoma was established. A right hemicoloctomy was performed. Final pathological examination confirmed LCNECC invading the muscularis propria, with lymph node metastases. The tumor was classified as pT2N1M0 (Stage III).
CLINICAL DISCUSSION
LCNECCs often mimic adenocarcinomas clinically, endoscopically, and radiologically. Pathological examination is the key for diagnosis. An immunohistochemical study using neuroendocrine markers is imperative to prevent overlooking the diagnosis of LCNECC.
CONCLUSION
LCNECCs represent rare aggressive carcinomas. Their diagnosis might be challenging. A better knowledge of this rare entities would enable early diagnosis.
PubMed: 38917703
DOI: 10.1016/j.ijscr.2024.109929 -
Translational Oncology Jun 2024Pancreatic ductal adenocarcinoma (PDAC) is associated with poor prognosis, wherefore targeted therapies have experienced increasing interest. Zolbetuximab is a novel...
PURPOSE
Pancreatic ductal adenocarcinoma (PDAC) is associated with poor prognosis, wherefore targeted therapies have experienced increasing interest. Zolbetuximab is a novel targeted therapy under investigation in patients with PDAC and targets Claudin 18.2 (CLDN18.2), which is a component of tight junctions and is of significance in various solid tumors. As its role in PDAC is not definitively elucidated, this study aims to clarify the significance of CLDN18.2 expression in PDAC in a real-world setting.
METHODS
All patients (n = 309) were recruited at one of the PANCALYZE study centers and received pancreatic resection with curative intention. Paraffin samples were analyzed using an antibody against CLDN18.2, which is known to be comparable to the antibody used by the SPOTLIGHT and GLOW studies.
RESULTS
94 PDACs are positive for CLDN18.2 (30.4 %). Positive CLDN 18.2 expression was associated with significantly better cancer differentiation (p < 0.001). Patients with positive CLDN18.2 expression showed significantly better overall survival when compared to patients with negative expression (median OS: 30 versus 18 months, p = 0.003). Additionally, in multivariable analyses, CLDN18.2 expression was identified as an independent factor for better survival in patients with PDAC (HR = 0.686, 95 %CI = 0.492-0.956, p = 0.026).
CONCLUSION
Significant improvement in survival could be demonstrated by adding Zolbetuximab to known chemotherapy regimes in patients with gastro-esophageal junction adenocarcinoma with at least 75 % CLDN18.2 positive cancer cells. Our findings demonstrate, that 30.4 % of the included patients with PDAC would potentially be eligible for therapy with Zolbetuximab in a real-world patient cohort. Results of trials targeting Claudin 18.2 are pending in patients with PDAC.
PubMed: 38917592
DOI: 10.1016/j.tranon.2024.102044 -
PloS One 2024Prostate stem cell antigen (PSCA) is associated with disease progression, promotion of angiogenesis, invasion, metastasis and immune evasion in cancer. However, its...
Prostate stem cell antigen (PSCA) is associated with disease progression, promotion of angiogenesis, invasion, metastasis and immune evasion in cancer. However, its expression pattern and diagnostic and prognostic potential have not been thoroughly analysed from a pan-cancer perspective. This study aimed to examine the effects of PSCA on the prognosis and inflammatory cell infiltration patterns of various cancer types. We analysed the relationship between PSCA expression and immunological subtypes in tumor microenvironment (TME) and the role of molecular subtypes, potentially promising immune biomarkers and tumour-infiltrating lymphocytes (TILs) in various cancer types, especially lung adenocarcinoma (LUAD). In addition, we investigated the prognostic significance of PSCA expression in LUAD. The co-expression network of PSCA was found to be mainly involved in the regulation of immune responses and antigen processing and expression and was significantly enriched in pathological and substance metabolism-related pathways in cancer. Altogether, this study reveals that PSCA is a promising target for immunotherapy in patients with cancer.
Topics: Humans; Antigens, Neoplasm; Prognosis; Tumor Microenvironment; Lymphocytes, Tumor-Infiltrating; Neoplasm Proteins; GPI-Linked Proteins; Biomarkers, Tumor; Neoplasms; Adenocarcinoma of Lung; Lung Neoplasms; Gene Expression Regulation, Neoplastic; Male
PubMed: 38917176
DOI: 10.1371/journal.pone.0298469