Objective: Calreticulin is a multicompartmental protein which regulates many important cellular responses. The aim of this study was to elucidate whether the intensity and location of calreticulin overexpression in tumor cells are related to the elevated humoral immunity to calreticulin in patients with benign or malignant breast disease. Methods: This study involved 27 patients with benign and 58 patients with malignant breast tumors before surgical resection and 38 healthy volunteers. Cytoplasmatic or membranous calreticulin overexpression in malignant or benign cells in paraffin-embedded tissues was determined using immunohistochemistry. Levels of the serum anti-calreticulin autoantibodies were detected by ELISA. Results: Statistically significant differences between serum levels of IgA of anti-calreticulin antibodies in controls and patients with breast tumors, and between controls and patients with nonmalignant breast diseases were found, but no statistically significant differences were found between levels of serum IgG anti-calreticulin antibodies. Humoral immunity to calreticulin developed against cytoplasmatic and co-localized membranous calreticulin was not correlated to the intensity of its overexpression and was present even in the absence of its membranous localization. Conclusions: The degree of calreticulin overexpression in lobular breast carcinoma is lower than in ductal breast carcinoma. Elevated concentrations of anti-calreticulin IgA antibodies were present more frequently in patients with metastasis in locoregional lymph nodes in comparison to anti-calreticulin IgG antibodies.

Background: Differentiated thyroid cancer (DTC) in children and adolescents is a rare but significant malignancy, often presenting at more advanced stages compared to adults, although it is associated with favorable long-term outcomes. This study aimed to identify prognostic factors and perform risk stratification with the goal of identifying low-risk patients who would benefit from a less radical treatment approach. Methods: This retrospective cohort study included patients aged 21 years and younger with DTC treated at the Institute for Oncology and Radiology of Serbia between 1980 and 2024. Results: The study analyzed 99 patients (39 children, 60 adolescents) with a median follow-up of 15.6 years (range: 0.6–43.6 years). No significant differences in long-term outcomes were observed between children and adolescents. Multivariate regression analysis identified a total number of more than 10.5 positive lymph nodes and extrathyroidal tumor extension as independent predictors of adverse events and event-free interval (EFI). Using these prognostic factors, patients were stratified into three groups: low-risk (no risk factors), intermediate-risk (one of two risk factors), and high-risk (both risk factors). Statistically significant differences in EFI were observed among the three groups. Notably, none of the patients in the low-risk group had evidence of disease after treatment. Patients classified as having no evidence of disease after treatment demonstrated significantly better EFI compared to those with evidence of disease. Conclusions: Our findings highlight the importance of meticulous risk stratification in predicting long-term outcomes and might serve as a basis for developing personalized therapeutic strategies. Identifying low-risk patients who may benefit from a less aggressive treatment approach while ensuring optimal treatment and follow-up for high-risk patients remains a central objective in the modern management of DTC.

Introduction: Radiation-induced breast angiosarcoma (RIBAS) is a rare adverse event associated with postoperative breast irradiation. The data from the literature indicate that RIBAS occurs in less than 0.3% of patients treated with adjuvant radiotherapy for breast cancer. Given the rarity, diverse clinical presentation, poor prognosis, and lack of consensus on the management, this study aimed to present experiences of our specialized cancer center with RIBAS, in terms of the incidence, presentation, management, and outcomes. Methods: We reviewed the medical records of 10,834 breast cancer patients treated at the Institute for Oncology and Radiology of Serbia between January 2013 and June 2024 to detect patients that had breast-conserving surgery, followed by postoperative irradiation, and developed angiosarcoma in the irradiated area at least 3 years after radiotherapy, without distant metastases. The incidence, latency period, management, and treatment outcomes were analyzed. Results: A total of nine female patients with RIBAS were identified and included in this study. The median age at RIBAS diagnosis was 64 years (range: 36–68), with a median latency of 64 months (95% CI > 57) from irradiation to diagnosis. The mean tumor size was 55 mm (SD 32.78). Patients were followed for a median of 30 months (range: 7–40) after initial RIBAS surgery. Local recurrence occurred in seven patients (77.8%), with five undergoing re-do surgery with curative intent. Three patients developed distant metastases during follow-up. The median overall survival (OS) was 31 months (95% CI > 30), with a 3-year survival rate of 15.2% (95% CI 2.5–91.6%). The median local recurrence-free interval was 10 months (95% CI > 3). Median OS after RIBAS local recurrence and after breast cancer treatment was 17 months (95% CI > 15) and 108 months (95% CI > 88), respectively. Conclusions: RIBAS is a rare but increasingly prevalent adverse event associated with BC irradiation, marked by an aggressive disease course and high relapse rates. Awareness, prompt diagnosis, and a radical surgical approach with wide clear margins are critical for improving patients’ outcomes.

E17549Background: Serum calcitonin level (sCT) is a precise marker for medullary thyroid carcinoma (MTC). However, lymph node (LN) metastases can be found in lower sCT. Further, preoperative ultrasound examination is not reliable enough for assessment of regional LNs. The aim of this pilot study was to analyze usefulness of sentinel lymph node (SLN) biopsy of jugulo-carotid chains, after methylene blue dye mapping procedure, for selection of clinically N0, but true-positive patients with micro-MTC for one-time modified radical neck dissection (MRND). Methods: This pilot study included 14 patients operated in our surgical clinic from 2007 to 2016th due to MTC with sCT lower than 1000pg/ml, tumors ≤ 10mm in size and clinically negative LNs. Patients with sCT > 1000pg/ml, larger tumors and cervical lymphadenopathy were excluded. All patients underwent total thyroidectomy and central neck dissection. SLN mapping was performed with intrathyroid subcapsular injection of 1%-methylene blue dye (0.2-0.5ml). Levels...

Objective: The aim of this study was to evaluate the relationship between the immunohistochemical score of cell proliferation index Ki-67 and steroid receptors in patients with a pathohistological diagnosis of breast cancer. The impact of neoadjuvant therapy on biological markers in breast cancer remains controversial. Methods: All patients with invasive breast cancer, as the primary and only malignancy, who underwent surgical and neoadjuvant therapy at the Institute of Oncology and Radiology of the Republic of Serbia (IORS) between 2017 and 2019 were included in the retrospective study. The expression level of Ki-67 and steroid receptors was detected by immunohistochemical analysis. Data were collected in an Excel database and analyzed in the statistical software SPSS program version 25. For statistical data processing Chi-squared test, KruskalWallis test, and Mann-Whitney U test were used. For all statistical analyses, a p <0.05 was considered statistically significant and a p≤0.001 was considered highly statistically significant. Results: The study included 190 patients with invasive breast cancer. The mean age of all patients at diagnosis was 57.2 ± 11.8 years. Among the patients, 64.2% are postmenopausal, 33.7% perimenopausal and 2.1% menopausal. There is a significant inverse correlation between the value of Ki-67 and the expression of steroid receptors. Conclusion: Ki-67 is an important biomarker in clinical practice for determining prognosis, residual risk, and response, and evaluating the effectiveness of neoadjuvant therapy. The results of our study revealed a correlation between high Ki-67 cell proliferative index values and lower steroid receptor expression values.

Objective: Papillary thyroid microcarcinoma (PTMC) often presents with multifocality and bilaterality, but the clinical significance of these features and their association with cervical lymph node metastases (LNMs) remain debated. The aim of this study was to investigate the patterns of multifocality and bilaterality in PTMC and their association with central and lateral neck lymph node metastases. Methods: This retrospective study analyzed 254 patients with histologically confirmed PTMC treated at the Institute for Oncology and Radiology of Serbia between 2004 and 2016. All patients underwent total thyroidectomy with central and, when indicated, lateral neck dissection. Associations between multifocality, bilaterality, and cervical LNM were evaluated using appropriate statistical tests. A p-value < 0.05 was considered statistically significant. Results: Multifocal tumors were present in 40.55% of patients, with bilateral involvement in 27.17%. Cervical LNM occurred in 33.07% of patients, with 26.77% showing central and 20.08% lateral metastases. Patients with multifocal tumors were associated with significantly higher proportions of male patients (p = 0.0283), higher rates of capsular invasion (p = 0.0002), larger tumor size (p = 0.0134), and increased incidence of LNM (p = 0.0152). Bilateral tumors were associated with larger tumor size (p = 0.0004) and more frequent capsular invasion (p = 0.0248), but not with a statistically significant increase in LNM. The number of tumor foci was strongly associated with both central and lateral LNM (p < 0.001). Conclusions: Multifocality, particularly with a higher number of tumor foci, is significantly associated with more aggressive tumor features and higher rates of cervical lymph node metastases in PTMC. While bilaterality also reflects a more aggressive phenotype, it was not independently predictive of LNM. These findings underscore the importance of careful risk stratification in PTMC and suggest that multifocality should inform surgical and follow-up strategies.