Ibrahim Halil Erdogdu

Homologous recombination deficiency (HRD) is a critical indicator of genomic instability; however, the composite HRD score may not reflect the distribution of distinct genomic scar components underlying this phenotype. In this exploratory study, we compared the absolute and relative contributions of loss of heterozygosity (LOH), large-scale state transitions (LST), and telomeric allelic imbalance (TAI) among solid tumors harboring pathogenic or likely pathogenic (P/LP) variants in BRCA1 or BRCA2. This retrospective study included 76 patients with solid tumors who underwent HRD testing between January 2023 and January 2026. P/LP variants in homologous recombination repair (HRR) genes, alongside LOH, LST, and TAI scores, were evaluated. The composite HRD score was calculated as LOH + LST + TAI, with values ≥ 56 defined as HRD-positive. Additionally, the relative contribution of each scar component to the total HRD score was determined. Given the small sizes of the BRCA1-only and BRCA2-only subgroups and the heterogeneity of the overall cohort, all gene-group comparisons were considered exploratory and hypothesis-generating. Overall, 21.1% of the cohort was HRD-positive. Patients harboring BRCA1/2 P/LP variants displayed a significantly higher median HRD score compared to non-carriers (47.0 vs. 30.0; p = 0.016). When comparing patients with tumors harboring BRCA1-only (n = 9) and BRCA2-only (n = 10) P/LP variants, LOH was higher in the BRCA2 group (19.0 vs. 5.0; p = 0.036); however, this difference did not retain statistical significance following false discovery rate (FDR) adjustment (q = 0.108). In an exploratory sensitivity analysis restricted to breast and ovarian tumors (BRCA1-only, n = 5; BRCA2-only, n = 9), the LOH/HRD ratio was higher in the BRCA2 group (0.301 vs. 0.000; p = 0.026; q = 0.039), whereas the LST/HRD ratio was higher in the BRCA1 group (0.488 vs. 0.310; p = 0.019; q = 0.039). These estimates were based on very small subgroups and should therefore be interpreted cautiously. This exploratory analysis identified differences in the relative distributions of LOH and LST between tumors harboring BRCA1-only and BRCA2-only P/LP variants, particularly in the breast/ovarian subset. However, the small and heterogeneous subgroups, together with the absence of systematic assessment of biallelic BRCA1/2 inactivation, preclude gene-specific or mechanistic conclusions. These observations should be regarded as hypothesis-generating and require validation in larger, tumor-specific, independent cohorts.

Background/Objectives: Endometrial cancer is a heterogeneous malignancy that displays distinct molecular features and clinical behaviors. The molecular profile of endometrial cancer and its relationship with menopausal status, histological subtype, tumor grade, mismatch repair (MMR)/microsatellite instability (MSI) status, co-mutation patterns, and TCGA molecular classification were investigated in the current study. Methods: A total of 81 histopathologically confirmed endometrial cancer cases were retrospectively evaluated. Molecular profiling was performed using a targeted 71-gene NGS panel together with MSI-PCR and mismatch repair (MMR) immunohistochemistry. Because the targeted panel was not designed to detect genome-wide copy-number alterations or comprehensive mutational signatures, molecular subgroup assignment was performed using a surrogate TCGA-inspired molecular classification approach based on POLE mutation status, microsatellite instability (MSI)/Mismatch Repair (MMR) findings, and TP53 alterations. Histological subtypes, tumor grades, menopausal status, and molecular alterations were compared. Results: Of the cases evaluated, 57 (70.4%) were endometrioid and 24 (29.6%) were serous carcinoma. TP53 variations were significantly higher in serous carcinomas compared to endometrioid tumors (66.7% vs. 26.3%; p = 0.001). In endometrioid carcinomas, the mean number of variants increased with advancing tumor grade (Grade 1: 4.44; Grade 2: 9.68; Grade 3: 11.42; p = 0.006). Alterations in BLM, CDC27, MLH3, and MSH3 were more frequently observed in high-grade tumors. In exploratory analyses, no significant differences were detected between the premenopausal and postmenopausal groups regarding total variant load, number of altered genes, MSI status, or the distribution of TCGA-inspired molecular subgroups; however, these comparisons were limited by the small number of premenopausal patients. The most frequent co-mutation was observed between BLM and CDC27 (55.6%). In the TCGA-inspired molecular classification, the most prevalent subgroup was NSMP-proxy (33.3%). Conclusions: Serous and endometrioid endometrial cancers display distinct molecular characteristics. In endometrioid carcinomas, the genomic alteration load increases in parallel with advancing tumor grade. TCGA-inspired molecular classification and co-mutation analyses revealed the prominent molecular heterogeneity of endometrial cancer. In exploratory analyses, no significant differences were detected between the premenopausal and postmenopausal groups regarding total variant load, number of altered genes, MSI status, or the distribution of TCGA-inspired molecular subgroups. However, these findings should be interpreted with caution because of the limited number of premenopausal patients. Given the limited number of premenopausal patients, findings related to menopausal status should be considered exploratory and require validation in larger, independent cohorts.

Background/Objectives: Breast cancer (BCa) is a heterogeneous disease with molecular and genetic characteristics that significantly influence prognosis and treatment strategies. Age-related differences in tumor biology may impact therapeutic decisions; however, data on somatic mutation profiles in geriatric patients are limited. Methods: This retrospective study included 371 BCa patients (53 geriatric ≥ 65 years, 318 non-geriatric) whose clinicopathological and next-generation sequencing (NGS) data were analyzed. Immunohistochemical markers and molecular subtypes were assessed according to ASCO/CAP guidelines. Mutational profiles were obtained using the QIAseq Human BCa Panel (93 genes). Results: Among all patients, 1669 somatic mutations were detected, and 93.3% of patients harbored at least one mutation. Mutation prevalence was similar between geriatric (96.2%) and non-geriatric (92.8%) groups (p = 0.526), indicating that age did not significantly affect overall mutational burden. The most frequently mutated genes were ATR, TP53, PIK3CA, PTEN, RAD50, BLM, NF1, AR, BRCA2, and KMT2C. Notably, PIK3CA mutations were significantly more frequent in geriatric patients (28.3% vs. 23.2%, p = 0.0418). TP53 mutations correlated with higher Ki-67 proliferation indices (p = 0.035), while ATR mutations were more common in HER2-enriched subtypes (p = 0.002). Conclusions: Our findings indicate that while the overall somatic mutational load in BCa does not differ significantly with age, specific molecular alterations—particularly the enrichment of PIK3CA mutations in elderly patients—underscore the importance of integrating genomic profiling into personalized treatment planning. This study represents the first comprehensive molecular characterization of geriatric BCa patients in Türkiye, providing valuable insights for age-specific genetic profiling, treatment optimization, and future multicenter translational studies.

Background: Breast cancer is the most commonly diagnosed neoplasm in women and is classified into different molecular subtypes based on the expression characteristics of estrogen and progesterone receptors (ERs and PRs) and human epidermal growth factor 2 (HER2, ERBB2): Luminal A, Luminal B, HER2(+), and triple-negative breast cancer (TNBC). Telocytes, a new type of stromal cell, provide structural support for the preservation of organ integrity and play a crucial role in the tumor microenvironment. In this study, we evaluated telocyte counts and expression profiles among breast cancer subtypes. Methods: The quantitative differences between telocytes in three subtypes of invasive breast cancer were assessed via immunohistochemistry, using vimentin, CD10, CD34, and c-Kit antibodies. Results: Vimentin(+), CD10(+), CD34(+), and c-Kit(+) telocyte counts were significantly higher in the Luminal and HER2(+) groups than in TNBC (p = 0.000 for vimentin, CD10, CD34, and c-Kit in Luminal vs. TNBC; p = 0.006 for CD34 in HER2(+) vs. TNBC). CD10(+), CD34(+), and c-Kit(+) telocyte counts were significantly higher in ER(+) than in ER(–) patients (p = 0.006, p = 0.000, and p = 0.009, respectively) and in PR(+) than in PR(–) patients (p = 0.018, p = 0.000, and p = 0.044, respectively). The presence of ER/c-Kit(+) telocytes was demonstrated, and c-Kit(+) telocyte counts were significantly lower in tumors larger than 5 cm than in those measuring 2–5 cm (p = 0.032). Conclusions: Our results showed quantitative differences and marker expression profiles for telocytes between different breast cancer molecular subtypes. c-Kit(+) telocytes may contribute to the regulation of tumor size.

Objective: The aim of this study is to investigate the usability of microRNA16-5P and 221-3P levels as biomarkers in determining thyroid cancers. Material and Methods: Patients who underwent thyroid surgery due to suspicious thyroid nodules were included in the study. A total of 142 patients who agreed to participate in the study had 3-5 cc venous blood taken into EDTA tubes and biochemistry tubes before the operation. In the postoperative period, 68 patients with malignant pathology results and 74 patients with benign pathology results were grouped as the control group. miRNA16-5p and miRNA221-3p levels were measured in serum samples taken from the patients. The levels of miRNA levels in malignant and benign patient groups were analyzed. Results: The miRNA 16-5p and miRNA221-3p levels of malignant patients were statistically significantly lower than those of benign patients (p

Background: Understanding PIK3CA mutations and co-mutations in non-small cell lung carcinoma (NSCLC) is critical to developing personalized treatment strategies. Therefore, this study aims to investigate PIK3CA mutations and the accompanying somatic variations in NSCLC. Methods: This retrospective study included 98 patients over 18 years of age who were diagnosed with NSCLC, operated on, and referred to the Molecular Pathology Laboratory between January 2019 and June 2024 for next-generation sequencing panel tests and ALK-ROS1 FISH analysis. Results: All patients were found to carry PIK3CA mutations. Among the 98 NSCLC patients analyzed, 16 (16.33%) were female and 82 (83.67%) were male. The average age of the patients was 64.53 ± 9.63 years, with an age range of 38–84 years, and the majority were 50 years or older. Of the cases, 51 presented the adenocarcinoma subtype, while the remaining 47 showed the squamous cell carcinoma subtype. A smoking history was present in 77 (78.57%) patients, while 21 (21.43%) had no smoking history. The most frequently detected pathogenic or likely pathogenic PIK3CA variations were c.1633G>A p.E545K (32.65%), c.1624G>A p.E542K (11.22%), c.3140A>G p.H1047R (11.22%), c.3140A>T p.H1047L (5.10%), c.1357G>C p.E453Q (4.08%), and c.3143A>G p.H1048R (2.04%). The top 10 mutations that most commonly accompanied PIK3CA variations were KRAS, NF1, TP53, EGFR, PTEN, BRAF, KIT, CDKN2A, SMARCA4, and ATM mutations, respectively. Conclusions: PIK3CA variations, along with other gene variations, may influence cancer progression and thus may play a crucial role in the determination of targeted treatment strategies.

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.

Menopausal status affects the prognoses and consequences of breast cancer. Therefore, this retrospective study aimed to reveal the molecular variation profile differences in breast cancer patients according to their menopausal status, with the hypothesis that the molecular variation profiles will be different at premenopausal and postmenopausal ages. Breast cancer patients (n = 254) who underwent molecular subtyping and QIAseq Human Breast Cancer NGS Panel screening between 2018 and 2022 were evaluated retrospectively. Their menopausal status was defined by age, and those aged 50 years and above were considered postmenopausal. Of the subjects, 58.66% (n = 149) were premenopausal and 41.34% (n = 105) were postmenopausal. The mean age at the time of diagnosis for all patients was 49.31 ± 11.19 years, with respective values of 42.11 ± 5.51 and 59.54 ± 9.01 years for the premenopausal and postmenopausal groups, respectively (p = 0.000). Among premenopausal patients, the percentages of patients in BCa subtypes (luminal A, luminal B-HER2(−), luminal B-HER2(+), HER2 positive, and triple-negative) were determined to be 34.90%, 8.05%, 26.17%, 10.74%, and 20.13%, respectively, while in the postmenopausal group, these values were 39.05%, 16.19%, 24.76%, 6.67%, and 13.33%, respectively (p > 0.05). Considering menopausal status, the distribution of hormone receptors in premenopausal patients was ER(+)/PgR(+) 63.76%, ER(−)/PgR(−) 23.49%, ER(+)/PgR(−) 10.74%, and ER(−)/PgR(+) 2.01%, respectively, while in postmenopausal women, this distribution was observed to be 74.29%, 23.81%, 1.90% and 0.00% in the same order (p = 0.008). The most frequently mutated gene was TP53 in 130 patients (51.18%), followed by PIK3CA in 85 patients (33.46%), BRCA2 and NF1 in 56 patients (22.05%), PTEN in 54 patients (21.26%), and ATR and CHEK2 in 53 patients (20.87%). TP53, PIK3CA, NF1, BRCA2, PTEN, and CHEK2 mutations were more frequently observed in premenopausal patients, while TP53, PIK3CA, BRCA2, BRCA1, and ATR mutations in postmenopausal patients. These findings contribute to a deeper understanding of the underlying causes of breast cancer with respect to menopausal status. This study is the first from Turkey that reflects the molecular subtyping and somatic mutation profiles of breast cancer patients according to menopausal status.

Malignant diseases occurring in elderly patients follow a different course from younger patients and show different genetic structures. Therefore, in this retrospective study, the somatic gene variant profile and fusion gene profiles of elderly and young acute leukemia patients were determined to draw attention to the existing genetic difference, and the results were compared. In this study, the records of 204 acute leukemia patients aged 18+ who were referred to the Molecular Pathology Laboratory from the Hematology Clinic between 2018 and 2022 were reviewed retrospectively. Fusion gene detection in patients was performed with the HemaVision^®-28Q Panel. The NGS Myeloid Neoplasms Panel was conducted using the MiniSEQ NGS platform according to the manufacturer’s protocol. When all cases are evaluated together, the most frequently diagnosed acute leukemia is acute myeloid leukemia (85.8%). Both groups had a similar fusion gene profile; however, the fusion burden was higher in the elderly group. When the groups were evaluated in terms of somatic gene variations, there were differences between the groups, and the variation load was higher in the elderly group. Considering the different somatic gene variation profiles, it is understood that the genetic structure of tumor cells is different in elderly patients compared to young cases.