Cervical carcinogenesis involves progressive molecular changes from preinvasive lesions to invasive carcinoma. Carboxypeptidase E (CPE) and aldehyde dehydrogenase 1A1 (ALDH1A1) have been implicated in cancer-related pathways, yet their stage-specific immunohistochemical expression patterns in cervical disease remain insufficiently characterized. This retrospective, specimen-based study assessed immunohistochemical expression of CPE and ALDH1A1 in cervical samples representing reactive/low-grade squamous intraepithelial lesions (LSIL), high-grade squamous intraepithelial lesions (HSIL), and invasive carcinoma. Staining was semi-quantitatively scored using standardized criteria. Group differences were analyzed with Kruskal-Wallis tests followed by post hoc comparisons, and monotonic trends across ordered disease stages were evaluated using the Jonckheere-Terpstra test. CPE expression differed significantly among disease groups, showing a stepwise increase from reactive/LSIL to HSIL and invasive carcinoma (P<0.001). Post hoc analyses confirmed higher CPE expression in HSIL and invasive carcinoma compared with reactive/LSIL lesions, with a further increase in invasive disease. ALDH1A1 expression did not differ between reactive/LSIL and HSIL groups but was significantly higher in invasive carcinoma. Trend analysis demonstrated significant monotonic increases for both markers across disease stages (P<0.001). This study provides a standardized, stage-specific immunohistochemical evaluation of CPE and ALDH1A1 in cervical lesions, highlighting progressive CPE upregulation and invasion-associated ALDH1A1 expression, and adds methodological clarity to the existing literature.

Objective: To investigate High Mobility Group Box 1 (HMGB1) expression in Wilms tumors and determine its relationship with clinicopathological factors and overall survival (OS), including stage-stratified survival analyses. Method: Forty-six Wilms tumor cases were retrospectively evaluated. Immunohistochemical expression of HMGB1 was recorded as the percentage of HMGB1-positive tumor cells. Associations with clinicopathological parameters were tested using chi-square/Fisher’s exact and non-parametric tests. OS was assessed with Kaplan-Meier analysis and log-rank testing. Exploratory analyses included HMGB1 tertiles and a simplified “HMGB1-low” vs. “HMGB1-other” grouping. Stage was analyzed as low stage (1-2) vs. high stage (3-5). Results: HMGB1 dichotomized using 5% and 10% cut-offs showed no significant associations with clinicopathological variables or OS (p-value>0.05). Stage 3-5 cases had significantly worse OS compared with stage 1-2 (log-rank p-value=0.049). In stage 1-2 tumors, very low HMGB1 expression (1-4%) was associated with significantly worse OS compared with HMGB1expression of ≥5% (log-rank p-value=0.024). This association was not observed in stage 3-5 tumors (log-rank p=0.858). Conclusion: In this study, HMGB1 expression was not an independent prognostic marker in the overall cohort. However, very low HMGB1 expression may identify a subgroup of early-stage Wilms tumor patients with unfavorable survival and deserves validation in larger-scale studies.

Objective:High mobility group box 1 (HMGB1) is a nonhistone chromatin-associated protein involved in chromatin remodeling, transcription, DNA replication, and repair. The purpose of this study was to assess the relationship between tissue expression of HMGB1, clinical outcomes, and histopathological characteristics in patients with breast cancer. Materials and Methods:The study included 282 patients with breast cancer. An in vitro diagnostic HMGB1 antibody was applied to the slides of tumor specimens. Results:Overexpression of HMGB1 was found in tumor cells of 123 (43.6%) patients. HMGB1 was only expressed in the nucleus in most tumors (88.7%), while in 32 (11.3%) tumors HMBG1 expression was cytoplasmic and/or extracellular. Severe inflammatory infiltration of the peritumoral stroma was observed in 76 (27%) patients. There was a correlation between remarkable inflammatory cell infiltration in the tumor microenvironment and HMGB1 overexpression, regardless of the molecular subtype, as well as the extranuclear location of HMGB1 expression (p = 0.023). HMGB1 expression was not found to be associated with overall or disease-free survival. However, axillary lymph node metastasis was significantly more common in tumors with intense inflammation (p = 0.024). Conclusion:The proportion of breast cancer patients with HMGB1 expression was lower in the present study than that reported previously. Furthermore, we did not detect a relationship between HMGB1 expression and prognosis. However, the relationship between HMGB1 expression and prognosis had been previously reported only in aggressive breast cancers. It is suggested that understanding the significance of HMGB1 expression in breast cancer may open new treatment opportunities, especially in aggressive and/or triple negative tumors.

Background: The survival rate among stomach adenocarcinoma patients is exceedingly low. NGAL (neutrophil gelatinase-associated lipocalin) has pivotal roles in cell proliferation, immunity, and tumorigenesis. KIM-1 (Kidney Injury Molecule-1), also referred to as TIM-1 and HAVcr-1, is a transmembrane glycoprotein located in healthy immune cells and epithelial cells, and its upregulated form is generally found in several human cancers. Aim: The aim of this study was to investigate the prognostic significance of the expression of KIM-1 and NGAL in stomach cancers and identify NGAL-positive inflammatory cells in the tumor microenvironment. Materials and Methods: We immunohistochemically evaluated the expression of NGAL and KIM1 in 172 cases of stomach adenocarcinomas. Result: The mean age of the patients was 64.07 ± 12.35 years, and the mean and median follow-up period were 25.5 and 20.3 months, respectively. The expression rates of KIM-1 and NGAL in tumor cells were identical at 31.4% (n = 54). In 27 of these cases, both proteins were present. Among the deceased patients, the rate of simultaneous KIM-1 and NGAL positivity was relatively higher (p = 0.041). NGAL-positive inflammatory cells were observed in 13.4% of cases, with no significant correlation between these cells and survival times (p = 0.497). However, there was a negative correlation between survival times and KIM-1 (p = 0.037) and NGAL (p = 0.016) expressions in tumor cells. Conclusions: The present study has shown that KIM-1- and NGAL-positive tumor cells are influential in gastric tumorigenesis. Given the progress in anti-KIM-1 therapy, the presence of KIM-1 expression could contribute to the development of new treatment options for aggressive gastric cancer. However, these discoveries need to be validated in larger-scale studies.

Background: Human epididymis protein 4 (HE4) was discovered in 1991 as a glycoprotein secreted from the cells of the human epididymal epithelium and associated with sperm development and immunity. Subsequent studies have shown that HE4 is also expressed in many normal tissues such as reproductive, respiratory, and digestive tract epithelia. Although the mechanism of action of HE4 in cancers is still unknown, its increased expression has been reported in many tumors, especially gynecologic malignancies. In our study, we have investigated the relationship between gastric carcinomas and increased HE4 expression. Materials and Methods: HE4 expression was studied in 114 formalin-fixed paraffin-embedded gastric carcinoma specimens and its association with different clinicopathologic parameters was evaluated. Results: Immunohistochemical HE4 expression was strong in 88 patients and weak in 26 of 114 patients. A significant correlation was found between HE4 staining intensities and five-year survival rates (p=0.002). There was no significant correlation between HE4 staining intensity and human epidermal growth factor 2 (HER2)/neu amplification, as well as other clinicopathologic data. Conclusion: This study has demonstrated the association of HE4 expression with 5-year survival in gastric tumors. In addition, although no significant correlation was found between HE4 staining intensity and HER2/neu amplification in our study, a significant correlation between these parameters has been reported in the literature. In conclusion, HE4, which we have found to be associated with long-term survival in our study, can be used as a prognostic marker in gastric cancers.

Introduction: Pancreatic ductal (PDACs), and ampullary (AACs) adenocarcinomas have different clinical and pathological prognostic features. The aim of our study is to comparatively evaluate the characteristic clinicopathologic features, prognostic factors and overall survival of resectable PDACs and AACs. Methods: We retrospectively compared a total of 120 patients with resectable adenocarcinomas stemming from main pancreatic duct, ampulla of Vater, and both regions in terms of prognostic clinicopathologic features and mean survival rates. Results: Adenocarcinomas (AC) originating from pancreatic ducts (n: 75) ,ampulla of Vater (n:19), and both of these anatomical (n:26) regions were pancreatobiliary (PB) (93.3%), intestinal (5.1%), and mixed ( 1.6%) histologic type tumors. There was no statistically significant difference between the tumor groups in terms of lymphovascular invasion (LVI) (p = 0.225), but perineural invasion (PNI) was seen at a statistically significantly lower rate in cases with AAC (p = 0.002). Lymph node involvement was seen more frequently in PDACs. A statistically significant intergroup difference was found when Pearson's chi-square test was used (p = 0.065). The median survival time was longer in AAC and stage I cases compared to those with PDAC and stage II-IV disease. Conclucion: In our study, tumor stage, perineural invasion and lymph node involvement were evaluated as important prognostic parameters in pancreatic and ampullary adenocarcinomas. A statistically significant difference was not detected between tumor groups regarding mean survival rates. Adenocarcinomas originating from the pancreatic head outside the ampullary region and also from the ampulla had independently poor prognostic factors closely comparable to PDACs.

Background: Trastuzumab is commonly utilized in the management of metastatic HER2-positive breast cancer. Our main goal was to examine the clinical outcomes and immune markers of patients who received trastuzumab and chemotherapy treatment. Methods: Between 1995 and 2012, a total of 98 patients diagnosed with metastatic HER2-positive breast cancer were retrospectively analyzed at Ege University Hospital and Tepecik Training and Research Hospital. The clinicopathological characteristics and clinical outcomes of the patients were assessed, and the associations between response rates, survival and the immune profiles of tumor infiltrating lymphocytes were statistically evaluated. Results: The average age of patients at the time of diagnosis was 50.1 +/- 10.3 (ranging from 30 to 79) years. The mean follow-up period for all patients was 97.9 +/- 53.8 months. Among the patients, complete response was observed in 24.5%, partial response in 61.2%, and stable disease in 8.2% of cases. The average progression-free survival was 50.3 +/- 26.9 months (ranging from 1 to 163 months), and the average overall survival was 88.8 +/- 59.4 months (ranging from 12 to 272 months). After analyzing all cases, it was found that patients who were younger (p=0.006), exhibited higher CD3-positivity (p=0.041), presented with higher FOXP3-positivity (p=0.025), showed complete or at least partial response to treatment (p=0.008), and experienced a long-term response to trastuzumab (and chemotherapy) treatment had longer survival (p=0.001). Conclusion: Patients with HER2-positive breast cancer, who initially respond positively to palliative trastuzumab and chemotherapy treatment, can achieve long-term tumor remission lasting for several years.

Abstract Purpose Trastuzumab is commonly utilized in the management of metastatic breast cancer. Our main goal was to examine the extended outcomes of patients experiencing a persistent positive response to trastuzumab treatment. Methods Between 1995 and 2012, a total of 98 patients diagnosed with inoperable, locally recurring or metastatic HER2-positive breast cancer were retrospectively analyzed at Ege University Hospital and Tepecik Training and Research Hospital. The clinical and pathological characteristics of the patients were assessed, and the associations between response rates, survival, and the immune profiles of tumor infiltrating lymphocytes were statistically evaluated. Results The average age of patients at the time of diagnosis was 50.1 ± 10.3 (ranging from 30 to 79) years. The mean follow-up period for all patients was 97.9 ± 53.8 months. Among the patients, complete response was observed in 24.5%, partial response in 61.2%, and stable disease in 8.2% of cases. The average progression-free survival was 50.3 ± 26.9 months (ranging from 1 to 163 months), and the average overall survival was 88.8 ± 59.4 months (ranging from 12 to 272 months). After analyzing all cases, it was found that patients who were younger (p = 0.006), exhibited higher CD3- positivity (p = 0.041), presented with higher FOXP3- positivity (p = 0.025), showed complete or at least partial response to treatment (p = 0.008), and experienced a prolonged response to trastuzumab treatment (p = 0.001) had longer survival. Conclusions Patients with HER2-positive breast cancer, who initially respond positively to palliative trastuzumab treatment, can achieve long-term tumor remission lasting for several years.