The immunohistochemical Galectin-3 expression in tumor and cancer-associated fibroblasts in invasive ductal carcinomas of breast and their relationship with clinicopathological parameters.

Background: Galectin-3 has an important role in metastasis, therefore, Galectin-3-focused therapies have attracted attention for various cancers. Aim: We aimed to reveal the relationship between the expression of Galectin-3 within the tumor/cancer-associated fibroblasts (CAF) and clinicopathological parameters in patients with invasive ductal carcinomas. Materials and Methods: Hematoxylin and eosin-stained slides of breast excision materials diagnosed between 2010 and 2016 were re-examined retrospectively. Accordingly, 118 cases (luminal group = 58, Human epidermal growth factor receptor 2 (HER2) group = 27, and triple-negative breast carcinoma group [TNBC] =33 cases) were included. Galectin-3 levels were evaluated with a calculated H-score in tumor and semiquantitatively in CAFs. Statistical Analysis: Data was analyzed with t-tests and Chi-square tests. Kaplan-Meier and Log-rank tests were used for survival analysis. Results: The presence of Galectin-3 expression in CAFs but not in the tumor was associated with the greater number of axillary metastatic nodes and advanced pN stage. The loss of Galectin-3 expression in CAFs was more frequent in TNBC. There was no significant relationship between the expression level of Galectin-3 and survival status. However, in most of the cases with distant metastasis or patients who died, Galectin-3 was negative in the tumor, whereas it was positive in CAFs. Conclusions: The expression of Galectin-3 in tumors and CAFs may have a role in metastasis to axillary lymph nodes and distant sites. In terms of molecular subtype, TNBCs show a relationship with Galectin-3 negativity in CAFs.

Ozone therapy as a novel complementary therapeutic approach in refractory idiopathic granulomatous mastitis.

Background: Autoimmunity may play a major role in the pathogenesis of idiopathic granulomatous mastitis (IGM). The therapeutic potential of ozone therapy has recently been shown in rheumatological diseases, and this study aimed to assess the clinical efficacy of ozone therapy (OT) in refractory IGM. Methods: Patients with biopsy-verified IGM and incomplete response after steroid therapy (n = 47) between 2018 and 2021 were enrolled. Of these, 23 cases in cohort A had standard treatment with further steroid therapy (ST), and 24 were treated with systemic OT via autohemotherapy (AHT) in addition to steroid therapy (cohort B). Results: The median age was 33 years (range, 24-45). Patients in cohort B had a higher complete response rate after completion of a four-month ozone therapy than those in the ST-group (OT-group, 37.5% vs. ST-group, 0%; p = 0.002). At a median follow-up of 12 months (range, 12-35), the patients treated with OT had a lower one-year recurrence in the affected breast than cases in cohort A treated with ST (OT-group, 21% vs. ST-group, 70%; p = 0.001). No significant side effects were observed in patients in cohort B related to AHT. Furthermore, OT significantly decreased the total steroid treatment duration (median week of steroid use; 26 weeks in cohort A vs. 12 weeks in cohort B; p = 0.001). Conclusion: Systemic OT increases the complete response rate and decreases the duration of steroid treatment in patients with refractory IGM. Therefore, ozone therapy is an effective, well-tolerated, and safe novel complementary therapeutic modality.

Expression of genes related to iron homeostasis in breast cancer.

BACKGROUND: The dysfunctions in the metabolism of iron have an important role in many pathological conditions, ranging from disease with iron deposition to cancer. Studies on malignant diseases of the breast reported irregular expression in genes associated with iron metabolism. The variations are related to findings that have prognostic significance. This study evaluated the relationship of the expression levels of transferrin receptor 1 (TFRC), iron regulatory protein 1 (IRP1), hepcidin (HAMP), ferroportin 1 (FPN1), hemojuvelin (HFE2), matriptase 2 (TMPRSS6), and miR-122 genes in the normal and malignant tissues of breast cancer patients. METHODS & RESULTS: The normal and malignant tissues from 75 women with breast malignancies were used in this study. The patients did not receive any treatment previously. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used in figuring the levels of gene expression associated with iron metabolism. When the malignant and normal tissues gene expression levels were analyzed, expression of TFRC increased (1.586-fold); IRP1 (0.594 fold) and miR-122 (0.320 fold) expression decreased; HAMP, FPN1, HFE2, and TMPRSS6 expressions did not change. FPN1 and IRP1 had a positive association, and this association was statistically significant (r = 0.266; p = 0.022). IRP1 and miR-122 had a positive association, and this association had statistical significance (r = 0.231; p = 0.048). CONCLUSIONS: Our study portrayed the important association between genes involved in iron hemostasis and breast malignancy. The results could be used to establish new diagnostic techniques in the management of breast malignancies. The alterations in the metabolism of malignant breast cells with normal breast cells could be utilized to achieve advantages in treatment.

Investigation of SRP9 protein expression in breast cancer.

BACKGROUND: Signal recognition particle (SRP) promotes co-translational translocation of the proteins through or into the endoplasmic reticulum membrane and it also has elongation arrest function. SRP9 is one of the six protein subunits of SRP and functions in elongation arrest activity by forming a heterodimeric structure with SRP14. It is one of the substrates of ADAR, which has been found to have a role in breast cancer. This study was conducted to investigate the SRP9 protein expression in normal and tumor tissues of patients with breast cancer and determine its prognostic significance. METHODS AND RESULTS: A total of 32 female patients who were diagnosed as having primary breast cancer and underwent surgery were included in the study. Western Blotting was performed to detect SRP9 protein expression levels in normal and tumor tissue samples. Clinical and pathologic characteristics were analyzed to assess the prognostic significance. SRP9 protein expression was statistically higher in the breast cancer tissue samples compared to normal matched tissue, and the mean SRP9 protein expression levels of breast cancer tissue normal tissue samples were 1.019 ± 1.011 and 0.551 ± 0.456, respectively (p = 0.001). SRP9 protein expression levels in tumor tissue of patients with lymph node metastasis, tumor size > 2 cm, estrogen receptor-positive, progesterone receptor-positive, and HER-2 negative were statistically higher than in normal tissue (p < 0.05). CONCLUSIONS: It is vital to clarify the roles of molecules such as SRP9 in understanding the pathogenesis of breast cancer. In our study, we showed that SRP9 expression increased in breast cancer and was associated with disease-related parameters.

Factors affecting pathological complete response after neoadjuvant chemotherapy in breast cancer: a single-center experience.

OBJECTIVE: The aim of this study was to examine the characteristics of patients admitted to our hospital with a diagnosis of breast cancer who reached pathological complete response after being operated following eight cycles of neoadjuvant chemotherapy. METHODS: Between 2015-2020, patients with pathological complete response who were operated on after neoadjuvant chemotherapy and sent to our clinic for radiotherapy were evaluated. RESULTS: The median age of the patients was 51 years. The most common histological type was invasive ductal cancer. The number of pathological complete response patients was 74 (28%), and the number of non-pathological complete response patients was 188 (72%). Patients with pathological complete response had a smaller tumor diameter than the non-pathological complete response group (p=0.001). For pathological complete response, T1 stage, N1 stage, NG 3, Ki-67 >20%, negative estrogen receptor, negative progesterone receptor, positive Cerb-B2, and adding trastuzumab to chemotherapy were statistically significant (p<0.05). Before neoadjuvant chemotherapy, stage T1-T2 (p=0.036), LN0-1 (p=0.026), Cerb-B2 positivity (p=0.025), and an initial nuclear grade of three (p=0.001) were found to be the factors affecting pathological complete response. CONCLUSIONS: With neoadjuvant chemotherapy, the size of locally advanced tumors decreases, allowing breast conserving surgery. The neoadjuvant chemotherapy response can be used as an early indicator of the prognosis of patients with breast cancer. Today, neoadjuvant chemotherapy is also used for patients with early-stage, operable breast cancer because it has been shown in many studies that reaching pathological complete response is associated with positive long-term results. If we can identify patients who have reached pathological complete response before neoadjuvant chemotherapy, we think we can also determine a patient-specific treatment plan at the beginning of treatment.

Factors affecting pathological complete response after neoadjuvant chemotherapy in breast cancer: a single-center experience

SUMMARY OBJECTIVE: The aim of this study was to examine the characteristics of patients admitted to our hospital with a diagnosis of breast cancer who reached pathological complete response after being operated following eight cycles of neoadjuvant chemotherapy. METHODS: Between 2015-2020, patients with pathological complete response who were operated on after neoadjuvant chemotherapy and sent to our clinic for radiotherapy were evaluated. RESULTS: The median age of the patients was 51 years. The most common histological type was invasive ductal cancer. The number of pathological complete response patients was 74 (28%), and the number of non-pathological complete response patients was 188 (72%). Patients with pathological complete response had a smaller tumor diameter than the non-pathological complete response group (p=0.001). For pathological complete response, T1 stage, N1 stage, NG 3, Ki-67 >20%, negative estrogen receptor, negative progesterone receptor, positive Cerb-B2, and adding trastuzumab to chemotherapy were statistically significant (p<0.05). Before neoadjuvant chemotherapy, stage T1-T2 (p=0.036), LN0-1 (p=0.026), Cerb-B2 positivity (p=0.025), and an initial nuclear grade of three (p=0.001) were found to be the factors affecting pathological complete response. CONCLUSIONS: With neoadjuvant chemotherapy, the size of locally advanced tumors decreases, allowing breast conserving surgery. The neoadjuvant chemotherapy response can be used as an early indicator of the prognosis of patients with breast cancer. Today, neoadjuvant chemotherapy is also used for patients with early-stage, operable breast cancer because it has been shown in many studies that reaching pathological complete response is associated with positive long-term results. If we can identify patients who have reached pathological complete response before neoadjuvant chemotherapy, we think we can also determine a patient-specific treatment plan at the beginning of treatment.

A Novel First-Line Treatment Alternative for Noncomplicated Idiopathic Granulomatous Mastitis: Combined Intralesional Steroid Injection with Topical Steroid Administration.

BACKGROUND: Idiopathic granulomatous mastitis (IGM) is a rare form of nonlactational mastitis. Due to the small number of case series and consequently inadequate prospective studies, there is still no consensus on the optimal treatment of IGM. In this study, we aimed to compare the efficacy of intralesional steroid injection with concomitant topical steroids to systemic steroid therapy only in the treatment of noncomplicated IGM. METHODS: Between June 2015 and April 2018, the patients' data was prospectively collected and analyzed retrospectively. The study included a total of 78 female patients diagnosed with IGM. Patients were divided into 2 groups: the local steroid treatment group (intralesional steroid injection with topical steroid administration; group 1, n = 46) and the peroral systemic steroid treatment group (group 2, n = 32). Response to the therapy, side effects, recurrence, the need for surgical treatment, and complication rates were compared. RESULTS: Forty-three patients (93.5%) in group 1 achieved a partial or complete response compared to 23 patients (71.9%) in group 2 after 3 months; this difference was significant (p = 0.012). The recurrence rates were significantly lower in group 1 (8.7%) compared to group 2 (46.9%; p = 0.001), and the need for surgical treatment was significantly less in group 1 (2.2%) than in group 2 (9.4%; p = 0.001). While the complication rates were similar between groups, a higher rate of systemic side effects was observed in group 2. CONCLUSION: Based on the results of our study, combined steroid injection and topical steroid treatment in IGM is as effective as systemic steroid treatment. We suggest that this combination therapy of topical steroids and local steroid injection should be used as first-line therapy in patients with noncomplicated IGM.

The Effect of Primary Surgery in Patients with De Novo Stage IV Breast Cancer with Bone Metastasis Only (Protocol BOMET MF 14-01): A Multi-Center, Prospective Registry Study.

BACKGROUND: More evidence shows that primary surgery for de novo metastatic breast cancer (BC) prolongs overall survival (OS) in selected cases. The aim of this study was to evaluate the role of locoregional treatment (LRT) in BC patients with de novo stage IV bone only metastasis (BOM). METHODS: The prospective, multicenter registry study BOMET MF14-01 was initiated in May 2014. Patients with de novo stage IV BOM BC were divided into two groups: those receiving systemic treatment (ST group) and those receiving LRT (LRT group). Patients who received LRT were further divided into two groups: ST after LRT (LRT + ST group) and ST before LRT (ST + LRT group). RESULTS: We included 505 patients in this study; 240 (47.5%) patients in the ST group and 265 (52.5%) in the LRT group. One hundred and thirteen patients (26.3%) died in the 34-month median follow-up, 85 (35.4%) in the ST group and 28 (10.5%) in LRT group. Local progression was observed in 39 (16.2%) of the patients in the ST group and 18 (6.7%) in the LRT group (p = 0.001). Hazard of death was 60% lower in the LRT group compared with the ST group (HR 0.40, 95% CI 0.30-0.54, p < 0.0001). CONCLUSION: In this prospectively maintained registry study, we found that LRT prolonged survival and decreased locoregional recurrence in the median 3-year follow-up. Timing of primary breast surgery either at diagnosis or after ST provided a survival benefit similar to ST alone in de novo stage IV BOM BC patients.

Impact of histone methyltransferase SUV420H2 in breast cancer.

Breast cancer is the most common type of cancer in women worldwide. Triple methylation of H4 lysine 20 (H4K20me3), a key component of epigenetic regulation of genomic integrity, is catalyzed by the methyltransferase, SUV420H2. Data on the expression status of SUV420H2 in breast cancer are limited. In the present study, the influence of SUV420H2 suppression on the proliferation of breast cancer cells was experimentally investigated. Subsequently, SUV420H2 expression was assessed in resectable breast cancer along with H4K20me3 status. SUV420H2 expression was knocked down in breast cells using small interfering RNA oligonucleotides. SUV420H2 expression was determined semi-quantitatively at the mRNA level. H4K20me3 was measured on extracted histone proteins using an approach similar to ELISA. Suppression of the SUV420H2 gene resulted in increased cell proliferation. Although the median SUV420H2 expression values were similar in tumor tissues and non-cancerous regions in the entire cohort (0.0022 and 0.0015, respectively; P=0.46), there was a notable difference in expression between tumor tissues and the adjacent non-cancerous region in the majority of patients. Increased SUV420H2 expression in tumors compared with healthy tissue was predominantly observed in patients with early-stage breast cancer, whereas reduced SUV420H2 expression was observed in tumors more frequently in patients with advanced stage diseases. There was no association between SUV420H2 expression and the tissue levels of H4K20me3. The results showed that SUV420H2 exhibited anti-proliferative activity in vitro, and exhibits a heterogeneous expression pattern in breast cancer tissues.

An investigation of the relationship between TMPRSS6 gene expression, genetic variants and clinical findings in breast cancer.

Breast cancer is one of the most common types of cancer among women worldwide. The TMPRSS6 (Transmembrane Serine Protease 6) gene encodes matriptase-2, which plays an important role in iron hemostasis as the hepcidin regulator and may play a role in breast cancer susceptibility. In this study, we examined the expression levels of the TMPRSS6 gene in healthy tissues and tumor tissues of breast cancer patients; and the relationship between these levels and pathological findings. The relationship between TMPRSS6 polymorphisms (rs733655, rs5756506, rs2413450, rs855791, rs2235324, rs4820268) and patients' hematological parameters. The gene expression study encompassed 47 breast cancer patients and the gene polymorphism study consisted of 181 breast cancer patients and 100 healthy controls. Gene expression analysis was performed by qRT-PCR. The genotyping of TMPRSS6 polymorphisms was performed by RT-PCR. TMPRSS6 gene expression levels in tumor tissues were found to be 1.88 times higher than the expression levels in the control tissues. We examined the relationship between TMPRSS6 gene expression levels and pathological data, statistically significant relationship was found between patient's estrogen receptor (ER) and HER2 findings and TMPRSS6 gene expression (respectively p = 0.02, p = 0.002). When the relationship between TMPRSS6 gene polymorphisms related genotypes distributions and hematological findings was investigated, a significant relationship was identified between mean corpuscular hemoglobin concentration (MCHC) parameter and the polymorphism of only the rs733655. According to our findings, the increase in TMPRSS6 gene expression in cancerous tissues shows that matriptase-2 may be effective in the cancer process. Thus TMPRSS6 gene polymorphisms may affect the disease process by affecting the blood parameters of patients.

Free/Total Serum Prostate-Specific Antigen Ratio in Women with Colorectal Cancer Has Prognostic Significance.

PURPOSE: The presence of prostate-specific antigen (PSA) in colon cancer tissues has been shown, but its clinical significance has not been known yet in colorectal cancer patients. We investigated the prognostic significance of percent free PSA value (free PSA/total PSA × 100) in female patients with colorectal cancer. METHODS: The serum concentrations of total and free PSA were measured by solid-phase two-site immunoradiometric assay in 184 patients. RESULTS: The cancer-specific survival (CSS) of patients with percent free PSA value ≥35 was significantly better compared to that of patients with percent free PSA value <35 (CSS rate was 82.9 and 55.5 %, respectively; log-rank x2 = 8135, p = 0.004). In multivariate Cox analysis, this percent free PSA threshold value had independent prognostic significance (relative risk 0.27, 95 % confidence interval 0.11-0.64, p = 0.003). CONCLUSION: Percent free PSA value, calculated by serum total and free PSA levels, has prognostic significance in women with colorectal cancer. The studies with larger patient series, utilizing ultrasensitive PSA assays whose lowest detection limit is lower, are required for a clearer understanding of this issue.

Benign mixed tumour of the breast and breast skin, two cases with diagnostic difficulties.

We present two cases of pleomorphic adenoma, one that developed in the breast parenchyma and the other in the breast skin, with their histopathological differential diagnosis.

Nodule-Forming Pseudoangiomatous Stromal Hyperplasia of the Breast: Report of Three Cases.

Pseudoangiomatous stromal hyperplasia (PASH) is a benign proliferative entity of mammary stroma. It is generally found as an incidental finding. It may rarely present as a palpable nodule. Three patients, who were 29, 45, and 58 years of age, were referred to our clinic with nodule and pain in the breast. The physical examinations and ultrasound findings of all three patients were consistent with fibroadenoma. Core biopsies were performed and reported as "benign breast parenchyma including stromal fibrosis." PASH areas were noted in one case. The excision specimens were observed as solid nodular masses with smooth external surfaces and white in colour. Microscopically, well-demarcated hyalinized stroma, including slit-like pseudovascular spaces lined by bland spindle cells, was observed. Immunohistochemically, these cells showed positive staining for CD34 and negative staining for CD31. Nodule-forming PASH mostly confuses with fibroadenoma with respect to clinical examination and radiological findings. Definite diagnosis requires histopathological verification. Differential diagnosis should be made with low grade angiosarcoma, fibroepithelial tumors, and myofibroblastoma.

Matrix-Producing Carcinoma of the Breast: Case Report.

Matrix-producing carcinoma (MPC) is an uncommon variant of metaplastic carcinoma. It was first described by Wargotz and Norris in 1989 as invasive breast carcinoma with direct transition to cartilaginous stroma without intervening spindle cell component. Since then, several studies, mostly in the form of case reports or case series, have been reported and the origin of tumor cell, importance of appropriate terminology for the tumor, histopathological differential diagnosis, benign breast lesions that the tumor could correlate with, and prognosis and consequently the treatment modalities have been discussed. A 43-year-old woman referred to our clinic with a lump in her left breast. Physical examination and radiological findings were consistent with malignancy. Core biopsy of the lesion was reported as "invasive breast carcinoma" and then breast-conserving surgery with sentinel lymph node dissection were performed. The case was diagnosed as MPC of the breast. The literature findings imply epithelial cell (ductal and/or myoepithelial) nature of this tumor. The prognosis is still controversial. Histopathological evaluation of sufficiently sampled surgical excision material is important to recognize and make a correct diagnosis.