Introduction: Absence of mismatch repair (MMR) genes in tumor cells or errors in the replication repair process may lead to DNA-MMR deficiency and microsatellite instability (MSI) formation. Specific tumor environments where gene variations are observed are believed to be conducive to the formation of MSI. This study aimed to determine the MSI status, MMR protein expression, and somatic mutation profile in solid organ tumors.Material and methods: In this study, the records of 192 patients with solid organ tumors who were referred to the Molecular Pathology Laboratory between January 2018 and December 2022 were reviewed retrospectively. The MSI profiles of the patients were evaluated using real-time polymerase chain reaction (PCR) and immunohistochemical (IHC) methods. Somatic variations in the patients were detected using an NGS colon cancer panel.Results: In the IHC evaluation, 22 cases showed MMR-deficient (dMMR) or high MSI (MSI-H), and 170 cases showed MMR-proficient (pMMR) or microsatellite stable (MSS). Real-time PCR results on the 22 dMMR cases revealed that 11 cases had MSI-H and 11 cases had MSS status. Among the 170 cases with pMMR, 160 cases were found to have MSS status, while 10 cases had low MSI (MSI-L). NGS analysis revealed that the three most frequent pathogenic variants in all cases were BLM exon 7 c.1544delA, MSH3 exon 7 c.1148delA, and MLH3 exon 2 c.1755delA. MSI-H cancer patients had a higher variation burden compared to MSS cancer patients. The most frequently observed pathogenic variant in both MSI-H and MSS cancer patients was BLM exon 7 c.1544delA.Conclusions: Our study covers not only colorectal cancer patients but also other solid tumor types, providing the first data from the Turkish population on the MSI-H/dMMR status and somatic mutation profile in the presence of this condition.

Background and Objectives: Small-cell lung cancer (SCLC) is an exceedingly aggressive neoplasm distinguished by an unfavorable prognosis. Recent studies have confirmed chemo-immunotherapy as the conventional first treatment for extensive-stage small-cell lung cancer (ES-SCLC), but the impact of treatment duration remains unclear. The goal of this study was to find out how the length of treatment affected progression-free survival (PFS) and overall survival (OS) in patients with ES-SCLC who were receiving first-line atezolizumab plus chemotherapy. Materials and Methods: This retrospective multicenter study comprised 82 patients from six oncology centers in Turkey between 2017 and 2024. Patients were categorized into two categories according to the quantity of chemotherapy cycles they had undergone: standard treatment (≤4 cycles) and extended treatment (≥5 cycles). For the purpose of analyzing survival outcomes and related clinical determinants, as well as the demographic structures and features of the patients, both univariate and multivariate Cox regression models were utilized. Results: The median number of atezolizumab cycles was 8 (1–63). OS was 29.46 months after 15.8 months of follow-up, while PFS was 10.63 months. When comparing the two groups, we found no statistically significant differences in either PFS (p = 0.952) or OS (p = 0.374). Significant associations with OS were seen in the standard therapy group for both ECOG PS 1 (p = 0.028). Thoracic radiation considerably decreased progression risk (HR = 0.41, p = 0.031) in the extended group. Conclusions: While prolonging chemo-immunotherapy beyond four cycles did not significantly improve survival, the selected patient subgroups may benefit from personalized approaches. Thoracic radiotherapy emerged as a key modifier of outcome.

Background/Objectives: Metastatic pancreatic cancer is a highly lethal disease, and clinically useful biomarkers for outcome stratification are limited. Uric acid reflects systemic metabolic stress and inflammatory signaling, suggesting potential relevance as a tumor–host biomarker. However, the clinical significance of uric acid-based composite biomarkers in pancreatic cancer remains unclear. Methods: In this multicenter retrospective cohort study, 110 patients with metastatic pancreatic adenocarcinoma treated between 2015 and 2024 were analyzed. Sex-adjusted uric acid-based biomarkers were calculated using uric acid z-scores normalized by sex and integrated with markers of nutritional and immune status, including the uric acid z-score-to-albumin ratio (UAzAR) and uric acid z-score-to-lymphocyte ratio (UAzLR). Associations with overall survival (OS), progression-free survival (PFS), and chemotherapy response were evaluated using Kaplan–Meier analysis, Cox proportional hazards models, receiver operating characteristic (ROC) analyses, and multivariate logistic regression. Results: The median OS and PFS for the entire cohort were 12.6 months (95% CI 11.3–13.9) and 7.5 months (95% CI 6.6–8.4), respectively. Patients with high UAzAR had significantly shorter OS than those with low UAzAR (7.3 vs. 16.4 months; log-rank p < 0.001), and similar findings were observed for UAzLR (7.4 vs. 16.4 months; p < 0.001). In multivariate Cox models, elevated UAzAR independently predicted inferior OS (HR] 3.10, 95% CI 1.58–6.09; p = 0.001) and PFS (HR 2.35, 95% CI 1.22–4.52; p = 0.010), while elevated UAzLR was similarly associated with reduced OS (HR 3.28, 95% CI 1.68–6.39; p < 0.001) and PFS (HR 2.47, 95% CI 1.30–4.70; p = 0.006). High UAzAR and UAzLR were also independently associated with chemotherapy failure (adjusted odds ratio [OR] 5.52, 95% CI 2.16–14.06 and OR 6.42, 95% CI 2.49–16.55; both p < 0.001). In ROC analyses, UAzAR and UAzLR demonstrated moderate discrimination for 12-month OS (AUC 0.659 and 0.658) and stronger discrimination for 6-month PFS (AUC 0.705 and 0.692). Conclusions: Sex-adjusted uric acid-derived composite biomarkers independently predict survival and chemotherapy response in metastatic pancreatic cancer and may identify a high-risk metabolic phenotype relevant for clinical risk stratification.

Background and Objectives: Pulmonary neuroendocrine carcinomas (NECs) are characterized by aggressive clinical behavior and heterogeneous postoperative outcomes. Early recurrence, often reflecting occult micrometastatic disease, remains a key determinant of prognosis and is insufficiently captured by conventional staging systems. We hypothesized that the lactate dehydrogenase-to-albumin ratio (LAR), as an integrative tumor–host biomarker, may provide biologically informed risk stratification in this setting. Materials and Methods: We conducted a multicenter retrospective cohort study including 88 patients with resected small cell lung cancer (SCLC) or large cell neuroendocrine carcinoma (LCNEC). Preoperative LAR and comparator inflammatory indices were evaluated. The primary endpoints were disease-free survival (DFS) and overall survival (OS), with early recurrence (≤12 months) as a prespecified secondary endpoint. Time-dependent receiver operating characteristic analyses, Cox proportional hazards models, and logistic regression analyses were applied within a predefined analytical framework. Results: Using a cut-off derived from 12-month DFS (LAR = 45.58), elevated LAR was associated with significantly shorter DFS (median 12.3 vs. 26.1 months; p = 0.018) and OS (median 20.7 vs. 52.8 months; p = 0.010). In multivariable analyses, LAR remained independently associated with both DFS (HR 1.012, 95% CI 1.001–1.023; p = 0.037) and OS (HR 1.016, 95% CI 1.005–1.027; p = 0.003). Elevated LAR was also associated with an increased risk of early recurrence (adjusted OR 4.656, 95% CI 1.520–14.262; p = 0.007). In time-dependent receiver operating characteristic (ROC) analyses, LAR demonstrated the highest overall discriminatory performance across evaluated biomarkers and showed a statistically significant advantage over neutrophil-to-lymphocyte ratio (NLR) for 24-month OS. Conclusions: Preoperative LAR captures a clinically relevant tumor–host phenotype associated with early disease progression and adverse survival outcomes in resected pulmonary NECs. As a biologically integrative and readily accessible biomarker, LAR may complement existing risk stratification strategies in this heterogeneous disease context. Prospective validation and integration into multimodal risk models are warranted.

Background/Objectives: The inflammatory burden index (IBI), calculated as C-reactive protein (CRP) multiplied by the neutrophil-to-lymphocyte ratio (NLR), has demonstrated prognostic value across several solid tumors. Its role in breast cancer, however, has not been investigated. This study evaluated whether pretreatment or post-treatment IBI could predict pathological complete response (pCR) in patients with HER2-positive or triple-negative breast cancer (TNBC) receiving neoadjuvant chemotherapy (NAC). Methods: This single-center retrospective study included 61 patients who completed NAC followed by surgery between 2019 and 2025. IBI was calculated before and after NAC, and the treatment-related change (ΔIBI) was assessed. Conventional inflammatory indices, including NLR, platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), C-reactive protein-to-albumin ratio (CAR), and absolute lymphocyte count (ALC), were evaluated for comparison. Analyses included Mann–Whitney U tests, paired Wilcoxon signed-rank tests, receiver operating characteristic (ROC) curve analysis, and multivariable logistic regression. Results: Twenty-nine patients (47.5%) achieved pCR. No pretreatment or post-treatment inflammatory index was significantly associated with pCR. In paired within-patient analysis, IBI increased significantly during treatment only in patients achieving pCR (p = 0.036), while remaining unchanged in the non-pCR group (p = 0.627). CAR showed an identical pattern, increasing exclusively in the pCR group (p = 0.013). This selective rise was not observed for any index lacking a CRP component and was independent of molecular subtype, anti-HER2 therapy, and chemotherapy regimen. On ROC analysis, ΔCAR yielded the highest area under the curve (AUC) among all inflammatory indices (0.637; p = 0.067), followed by ΔIBI (0.606; p = 0.157); neither reached statistical significance. Ki-67 was the only independent predictor of pCR (AUC 0.724; p = 0.003; optimal cutoff ≥25%). Conclusions: This is the first study to evaluate IBI in HER2-positive and TNBC receiving NAC. Static IBI values did not predict pCR. The selective rise in IBI and CAR during treatment in patients achieving pCR—two independently formulated CRP-based indices showing an identical pattern—suggests that the CRP component carries the biologically relevant signal. This hypothesis-generating observation warrants prospective validation in larger cohorts.

Ejmi Eurasian Journal of Medical Investigation