The Clinical and Pathological Characteristics That Differentiate Cases With "Low Estrogen Receptor Expression" From Triple-Negative Breast Cancer.

Objective: Estrogen receptor (ER) expression is an immunohistochemical marker that is examined in all invasive breast cancers and has prognostic and predictive value. ER-positive breast cancers refer to those that show positivity for ER at 1% cellular expression or higher. The American Society of Clinical Oncology/College of American Pathologists guidelines suggest using the term "low ER-positive breast cancer" for tumors with ER expression between 1% and 10%. Low ER-positive breast cancers exhibit similarities, in terms of disease-free survival and overall survival rates, to triple-negative breast cancers (TNBCs) rather than ER-positive breast cancers. In this study, our aim was to compare the clinicopathological characteristics of low ER-positive breast cancer cases diagnosed and followed in our clinic with TNBCs. Materials and Methods: A total of 26 cases of low ER-positive breast cancer diagnosed at University of Health Sciences Turkey, Izmir Tepecik Training and Research Hospital between 2010 and 2016 were retrieved from hospital records. The relevant histopathology slides and blocks were retrieved and re-evaluated retrospectively through microscopic examination. Thirteen cases that met the criteria were included in the study. Additionally, a consecutive series of 13 TNBC cases that did not receive neoadjuvant treatment within the same time period were identified. Results: In the low ER-positive group, the presence of tumor necrosis, as well as histological grade, nuclear grade and Ki-67 proliferation index were significantly lower compared to the TNBC group. Ductal carcinoma in situ (DCIS) was significantly more common in the low ER-positive group compared to the TNBC group. There were no significant differences between the two groups in terms of tumor size, histological tumor type, axillary lymph node involvement, tumor margins, peritumoral and intratumoral inflammation, local recurrence, distant metastasis, survival, and other characteristics. Conclusion: Although our study consisted of a small number of cases, some features showed significant differences between low ER-positive breast cancers and TNBCs. Histological and nuclear grades, as well as the presence of a DCIS component, were associated with low ER-positive breast cancer. In contrast, the presence of tumor necrosis, as well as Grade 3 features and a high Ki-67 proliferation index indicated TNBC.

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.

The Relationship of Pseudoangiomatous Stromal Hyperplasia (PASH)-Like Appearance in Invasive Breast Carcinomas with PASH Areas in Non-Tumoral Breast Parenchyma as Well as on Axillary Lymph Node Involvement.

Objectives: The aim of this study were to determine the relationship of pseudoangiomatous stromal hyperplasia (PASH)-like appearance in invasive breast carcinomas (IBCs) with PASH foci in the non-tumoral breast parenchyma as well as axillary lymph node involvement. Methods: In this study, 200 consecutive cases with IBC were re-examined. Cases with and without PASH-like appearance in IBC were determined. Each case was assessed regarding the presence of accompanying PASH foci (CD34+, CD31-) in the non-tumoral areas in addition to other clinicopathological parameters. Results: PASH-like appearance within the IBC was present in 22 of the 200 cases (11%) and absent in 178 (89%). The presence of PASH foci in the non-tumoral breast parenchyma was significantly more common in IBC with PASH-like appearance compared to the group without such areas. However, there was no significant difference between the groups regarding other clinicopathological parameters (age, tumor size, nuclear and histological grade, Estrogen receptor/Progesterone receptor status, HER2 status, and Ki-67 proliferation index), lymphovascular invasion (LVI), and axillary lymph node involvement. There was no significant difference between the two groups regarding the histopathological findings observed in the non-tumoral areas. Conclusion: PASH-like appearance within IBC was found to be associated with higher rate of PASH foci in the non-tumoral breast parenchyma. However, such cases do not show a difference as regards LVI and axillary lymph node metastasis.

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.

Relationship of E-cadherin, Beta-catenin, N-cadherin, ZEB1 and αSMA as Epithelial Mesenchymal Transition markers with prognostic factors in early and advanced stage laryngeal squamous cell carcinomas.

Aims: To investigate the relationship between E-cadherin, beta-catenin, N-cadherin, ZEB1, and αSMA as epithelial-mesenchymal transformation markers with tumor stage, lymph node metastasis (LNM), and overall survival (OS) in laryngeal squamous cell carcinomas (LSCC). Materials and Methods: A total of 100 cases diagnosed with LSCC were included in the study. Data about the lymphovascular invasion (LVI), perineural invasion (PNI), necrosis, and LNM were recorded by evaluating hematoxylin-eosin-stained slides. Markers of E-cadherin, beta-catenin, N-cadherin, ZEB1, and αSMA were applied to the sections prepared from paraffin blocks of tumor samples. Results: Ninety-five male and five female patients were included in the study, and 38 of them exited. A significant relationship was observed between OS with advanced tumor stage, presence of LNM and PNI. A significant relationship was found between increased tumor Zeb1 expression and advanced tumor stage. In univariate and multivariate analyses, a significant negative relationship with OS, and increased Zeb1 expression in tumor and tumor stroma was seen. Any relationship was not observed between E-cadherin, beta-catenin, N-cadherin, and αSMA and OS. Conclusion: Among the EMT markers, we evaluated in our study, it was seen that Zeb1, which is an EMT transcription factor, is associated with tumor stage, LNM, and OS. Remarkably, Zeb1 expression observed in tumor stroma was also significant for OS. Any similar data reported for LSCCs have not been encountered in the literature, and it was thought that it would be appropriate to support our findings with further studies to be performed on this subject.

Villoglandular Pattern in HPV-associated Endocervical Adenocarcinoma is Associated With Excellent Prognosis: A Reappraisal of 31 Cases Using IECC and Silva Pattern Classification.

Villoglandular adenocarcinoma of the cervix is a rare histologic entity that typically develops in young women, characterized by an association with oral contraceptives and excellent prognosis, though this point is controversial. These tumors have not been studied in the context of the International Endocervical Adenocarcinoma Criteria and Classification (IECC) or Silva Pattern Classification. We analyzed 31 cases that met strict diagnostic criteria, including being completely excised with negative margins. These were categorized according to IECC and Silva Pattern Classification and the association with various pathologic parameters analyzed. Most patients were young with a mean age of 41.1 (range 25-79). There were 14 (45.2%) pattern A, 11 (35.5%) pattern B, and 6 (19.3%) pattern C cases. Only 1 of 22 patients (4.5%) presented with lymph node metastasis at the time of diagnosis (pattern C, stage IB1) and 3 (9.7%) had lymphovascular invasion (2 pattern C, 1 pattern B). Overall survival was 100%, while recurrence-free survival was 96.2% for the entire cohort with only 1 case (3.2%) recurring 25 mo after surgery (IB2, pattern B). Kaplan Meier analysis (log rank test) revealed no significant correlation for recurrence-free survival at 5 and 10 yr associated with depth of invasion, tumor size, Silva pattern, FIGO stage, lymphovascular invasion, or lymph node metastasis. Cox univariate analysis demonstrated no independent prognostic factors predicting recurrence-free survival. These results indicate that completely excised villoglandular adenocarcinoma generally has an excellent prognosis and when Silva Pattern Classification is applied, those tumors that potentially have a higher chance for adverse outcomes can be identified.

The Clinicopathologic Features of 22 Cases With Primary Invasive Papillary Carcinoma of the Breast Identified in 1153 Cases With Invasive Breast Carcinoma: Single-Center Experience.

Objective: Invasive papillary carcinoma (IPC) of the breast is an uncommon histologic subtype with limited data in the literature. The aim of this study was to increase the evidence base by presenting clinicopathological findings of cases diagnosed as IPC. Materials and Methods: Hematoxylin and eosin sections and immunostaining of surgical excision specimens diagnosed as invasive breast carcinoma were re-evaluated, retrospectively. Results: IPC was detected in 22 cases (1.9%), of which 7 (0.6%) had pure and 15 (1.3%) had mixed morphology. Histologic types accompanying IPC were: Invasive ductal carcinoma (IDC) (15/15); invasive micropapillary carcinoma (3/15); and pleomorphic lobular carcinoma (1/15). Patient ages ranged between 36 and 89 (median 56.5) and the tumor size from 8 to 70 mm (median 19 mm). The histologic grade was 3 in five cases, 2 in 13, and 1 in four cases. The nuclear grade was 3 in 10 cases and 2 in 12. The values of positivity for estrogen receptor, progesterone receptor, human epidermal growth factor receptor-2, and Ki-67 index indicated Luminal B phenotype in 16 (72.7%), triple-negative in 5 (22.7%), and Luminal A in 1 case (4.6%). Ductal carcinoma in situ was noted in 19 cases (86.4%). Conclusion: IPC was mostly detected as an accompanying carcinoma to IDC at postmenopausal ages and was mostly Luminal B phenotype with intermediate-to-high grade features.

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.

Invasive Breast Carcinoma with Abundant Collagenous Stroma Shows Lower Level of CD68-Positive Tumor Associated Macrophages than Those of Invasive Carcinoma without Abundant Collagenous Stroma.

BACKGROUND AND AIM OF THE WORK: The significance of association between cancer and its stromal microenvironment has been recognized. We aimed to investigate the immunohistochemical staining features of D2-40 (podoplanin), SMA (smooth muscle actin) and CD68 (pan-macrophage marker) in patients with early stage invasive breast cancer with/out peritumoral PASH-like stroma. METHODS: The H&E sections of core needle biopsy specimens of invasive breast carcinomas diagnosed during one-year time period were reviewed in terms of the presence of accompanying PASH-like stroma retrospectively. Cases with similar pattern of growth in their surgical excision materials were included. Eight cases were grouped as 'Invasive tumor with PASH-like stroma' and 21 cases as 'Invasive tumor without PASH-like stroma', consecutively. The results of immunohistochemical staining for D2-40, SMA and CD68 were noted semiquantitatively as 'negative','weak', moderate' or 'strong'. RESULTS: CD68 was found significantly lower in invasive tumor with peritumoral PASH-like stroma than those of tumor without PASH-like stroma. No significant differences were found for SMA and D2-40 between two groups.  Conclusions: Tumor-associated macrophages (CD68 positive) in tumor stroma have been demonstrated in association with tumor behavior in several studies. The presence of peritumoral PASH-like stroma, which is poorly staining for CD68, might be a morphological clue for the behavior of tumor.

The Expression of Galectin-3 in Tumor and Cancer-Associated Fibroblasts in Invasive Micropapillary Breast Carcinomas: Relationship with Clinicopathologic Parameters.

OBJECTIVE: Galectin-3 affects tumor progression and cell surface polarization by expressing from the tumor and cancer-associated fibroblasts (CAFs). Therefore, it may have a role on micropapillary carcinomas (IMPC), which have characteristic morphological features. The aim was to investigate the expression levels of Galectin-3 within tumor and peritumoral CAFs in IMPC, and to compare with expression in invasive ductal carcinomas (IDC). MATERIALS AND METHODS: Hematoxylin and Eosin-stained preparations of resection materials examined between 2010-2016 were re-evaluated. Thirty-four IMPC cases and 34 IDC cases with similar molecular subtype distribution to IMPC were compared. Galectin-3 levels were evaluated with a calculated H-score in tumor and semi-quantitatively in CAFs. RESULTS: While tumoral Galectin-3 expression levels were higher in IMPCs compared to IDCs, there was no difference for Galectin-3 expression in CAFs between the two histologic types. However, there was no significant relationship between tumoral Galectin-3 expression and clinicopathological parameters in IMPCs. When the subjects were divided into two groups, depending on their Galectin-3 status regardless of histological types, the loss of Galectin-3 expression in tumor was found to be related to larger tumor size/advanced pT stage and a greater number of metastatic nodes. Additionally, expression of Galectin-3 in CAFs was found to be associated with distant metastasis. CONCLUSION: IMPC showed prominent Galectin-3 expression in tumor compared to IDC. However, independent from the histological type, whereas the loss of Galectin-3 expression in tumor showed an association with larger tumor size and higher number of metastatic axillary lymph nodes, the presence of Galectin-3 expression in CAFs showed an association with distant metastasis.

A Nobel-Winning Scientist: Aziz Sancar and the Impact of his Work on the Molecular Pathology of Neoplastic Diseases.

Aziz Sancar, Nobel Prize winning Turkish scientist, made several discoveries which had a major impact on molecular sciences, particularly disciplines that focus on carcinogenesis and cancer treatment, including molecular pathology. Cloning the photolyase gene, which was the initial step of his work on DNA repair mechanisms, discovery of the "Maxicell" method, explanation of the mechanism of nucleotide excision repair and transcription-coupled repair, discovery of "molecular matchmakers", and mapping human excision repair genes at single nucleotide resolution constitute his major research topics. Moreover, Sancar discovered the cryptochromes, the clock genes in humans, in 1998, and this discovery led to substantial progress in the understanding of the circadian clock and the introduction of the concept of "chrono-chemoterapy" for more effective therapy in cancer patients. This review focuses on Aziz Sancar's scientific studies and their reflections on molecular pathology of neoplastic diseases. While providing a new perspective for researchers working in the field of pathology and molecular pathology, this review is also an evidence of how basic sciences and clinical sciences complete each other.

The Effect of the Extent of Neuroendocrine Differentiation on Cytopathological Findings in Primary Neuroendocrine Neoplasms of the Breast.

OBJECTIVE: This study aimed to describe the cytological features of neuroendocrine breast tumors and to show the effect of the extent of neuroendocrine differentiation on cytological features. METHODS: Breast tumor excision materials showing immunostaining with neuroendocrine markers (Synaptophysin or Chromogranin A) were determined and divided into two groups: cases with focal (10%-50% of tumor cells) staining and cases with diffuse (>50% of tumor cells) staining. A group of cases without neuroendocrine features/staining was used as control group. Fine needle aspiration biopsy specimens of the tumor mass or metastatic lymph nodes were examined and compared. RESULTS: Twenty cases with neuroendocrine differentiation were included. Eleven cases were in the diffuse group, nine cases were in the focal group. Clean background, high cellularity, loosely cohesive cell groups with monotonous appearance, and naked nuclei were more common in the diffuse group. On the contrary, tight cohesive cell groups, the proportion of large cells, nuclear pleomorphism, and nucleolar prominence were higher in the group with focal staining. Plasmocytoid appearance, isolated cell groups, and binucleation were in similar distribution in both groups. Although round-oval nuclei were dominant in both groups, round nuclei were observed to be slightly more in the diffuse group. Only two cases in diffuse group showed cytoplasmic granularity and one case in focal group showed necrosis and mitosis. In the control group, tight cohesive groups, large cell size, pleomorphism, prominent nucleoli, and coarse chromatin were more commonly encountered. CONCLUSIONS: Clean background, hypercellularity, loss of cohesion, naked nuclei, monotonous cells with round nucleus, and granular cytoplasm were more prominent in cases showing diffuse staining with neuroendocrine markers. Suspecting neuroendocrine differentiation in tumors that show focal staining with neuroendocrine markers can be challenging in cytological preparations.

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.

Pathology and Biobanking.

Biobanks are units where high quality and long-term protection of biomaterials is maintained. This system, in which biological materials and data are systematically recorded and stored, is a unique resource for the study of the pathophysiology of disease, the development of diagnostic biomarkers, and working with human tissues for the potential discovery of targeted therapeutic agents. At this point, the pathology unit plays a unifying and complementary role between the clinical and core disciplines and offers optimal management of the patients' biomaterials for diagnostic and research projects. The aim of this article is to present general information with regard to a biobank constructed for the storage of tumor tissue and blood biospecimens. Ethical issues (informed consent, protection of confidentiality and privacy, and secondary use of biospecimens) and the information technology system (collection, systematic recording, backup and protection of clinical information) are important issues in biobanking. The selection of freezers to be used in storage (mechanical freezers, liquid-vapor nitrogen tanks), and if mechanical freezers are preferred the establishment of the relevant infrastructure and support team (such as additional power units for protection from power outages), the preservation of materials by aliquoting in different freezers, ensuring financing so as to afford the cost of the infrastructure, and implementation of all these dynamics while adhering to international guidelines are of the utmost importance.

The association of 18F-fluorodeoxyglucose PET/computed tomography parameters with tissue gastrin-releasing peptide receptor and integrin αvß3 receptor levels in patients with breast cancer.

OBJECTIVE: Gastrin-releasing peptide receptor (GRPR) and integrin αvß3 receptors are significantly associated with primary breast cancer, neovascular endothelial, and metastatic tumor cells. We aimed to evaluate GRPR and integrin αvß3 receptor staining, F-FDG uptake patterns and possible prognostic factors in breast cancer. METHODS: Ninety lesions of 87 subjects diagnosed with breast cancer were included in this prospective study. The sections were stained with GRPR and integrin αvß3. Subjects were divided into four molecular subgroups: luminal A, luminal B, triple negative and HER2. PET/CT imaging was performed on all subjects. The groups were compared in terms of GRPR and integrin αvß3 staining properties, possible prognostic factors and mean SUVmax values. RESULTS: Increased F-FDG uptake was significantly associated with estrogen receptor and progesterone receptor negativity. Molecular subtypes were significantly associated with mean integrin scores (P = 0.030), while histopathological subtypes were significantly associated with mean GRPR scores (P = 0.029). Increased integrin αvß3 expression is significantly associated with ER and PR negativity. Additionally, GRPR score was significantly correlated with estrogen receptor and progesterone receptor expression scores and a negative statistically significant correlation was detected between integrin and progesterone receptor scores. Mean primary lesion SUVmax had a statistically significant positive correlation with integrin αvß3 score. CONCLUSION: GRPR and integrin αvß3 expression results are complementary to F-FDG PET/CT findings, and are also significantly correlated with hormone receptors associated with aggressive subtypes. These results may pave the way for GRPR and integrin αvß3 targeted imaging with Ga-labeled molecules and systemic radionuclide treatment with Lu-labeled compounds.

Histopathological and Clinical Differences Between Primary Breast Carcinomas With Neuroendocrine Features and Primary Breast Carcinomas Mimicking Neuroendocrine Features.

We aimed to determine the histopathological differences between primary breast carcinomas with neuroendocrine features (NEBC) and carcinomas mimicking neuroendocrine features (NEBC-like). Twenty-three cases with NEBC, all showing positive staining for synaptophysin and/or chromogranin-A in ≥50% of tumor cells and 36 cases with NEBC-like (no staining for neuroendocrine [NE] markers but suspicious for NE morphology in terms of solid/trabecular growth patterns) were included in the study. Significant differences were found between the groups in terms of the patients' ages, histologic/nuclear grade of tumor, lymphovascular invasion, comedo-type ductal carcinoma in situ (DCIS), microcalcification, Ki-67 proliferation index, nuclear shape, and level of peritumoral lymphocytic infiltration. The presence of large-size solid cohesive groups of tumor cells; plasmocytoid, spindle, and/or columnar shapes of tumor cells; and eosinophilic-granular appearance of cytoplasm were mostly noted in the NEBC group. The presence of small- to medium-sized solid cohesive groups of tumor cells; high-grade histologic and nuclear features; clear cytoplasm; and round to ovoid nucleus were mostly noted in the NEBC-like group. No significant differences were found in terms of tumor size, ER/PR/HER2 status, as well as the presence of DCIS, elastosis, extracellular/intracellular mucin, signet ring cells, apocrine features, and accompanying papilloma or ductal ectasia. In conclusion, small- to medium-sized solid cohesive groups of tumor cells, high-grade features, clear cytoplasm, round to ovoid shape of nucleus, lymphovascular invasion, comedo-type DCIS, microcalcification, high level of Ki-67 proliferation index (≥20%), and moderate/strong level of peritumoral lymphocytic infiltration might support non-NE features in breast carcinomas.

CD10, TDAG51, CK20, AR, INSM1, and Nestin Expression in the Differential Diagnosis of Trichoblastoma and Basal Cell Carcinoma.

BACKGROUND: Trichoblastoma (TB) and basal cell carcinoma (BCC) are 2 different neoplasms composed of basaloid cells and have overlapping histopathological features. We compared the immunoexpression of CD10, T-cell death-associated gene 51 (TDAG51), cytokeratin 20 (CK20), androgen receptor (AR), insulinoma-associated protein 1 (INSM1), and nestin for the differential diagnosis of these tumors. MATERIALS AND METHODS: We assessed a total of 27 BCC and 27 TB cases, including 4 TB lesions in nevus sebaceous and 3 malignant TB lesions for CD10, TDAG51, CK20, AR, INSM1, and nestin expression. RESULTS: Staining for CK20, TDAG51, INSM1, and stromal CD10 was significantly more common in TB cases than in BCC cases ( P < .001). Epithelial CD10 and AR staining was significantly more common in BCC cases than in TB cases ( P < .001). The difference between the groups for nestin staining was not significant ( P > .05). Stromal CD10 staining was the most sensitive marker (96.3%) and INSM1 the least sensitive (55.6%) marker for TB. TDAG51 showed 100% specificity for TB. A larger number of CK20 positive cells was found in the cases associated with nevus sebaceous than in the other TBs. CONCLUSION: All the selected markers except nestin were useful for the differential diagnosis between TB and BCC. CD10 and TDAG51 were more useful than the other markers. The use of CK20 could be preferred in nevus sebaceous lesions. INSM1 was less effective in highlighting Merkel cells within the lesion than CK20.

Preventive role of superoxide dismutase on radiation-induced periprosthetic capsule development.

BACKGROUND: Capsule fibrosis is the most important and annoying complication of breast implant surgery. Radiotherapy (RT) used in the local treatment of breast cancer has an increasing effect on the existing fibrous capsule; this is called radiation-induced fibrosis (RIF). In this randomized controlled experimental study, we aim to investigate the reduction effect of superoxide dismutase (SOD) on RIF. METHODS: Sprague-Dawley rats were randomized into four groups, all of which were subjected to implant surgery. No additional procedures were done for the control group. The other groups were the SOD group, the RT + SOD group, and the RT group. The capsules were evaluated histopathologically. RESULTS: Although SOD reduced surgery-induced capsule formation, it neither prevented nor reduced significantly RIF. CONCLUSIONS: In an experimental model that resembled breast cancer treatment, we concluded that SOD cannot reduce RIF but is effective in reducing capsular fibrosis around the silicone after implant surgery.

Primary breast carcinomas with neuroendocrine features: Clinicopathological features and analysis of tumor growth patterns in 36 cases.

Primary breast carcinoma with neuroendocrine features (NEBC) is an uncommon tumor. In the classification of WHO 2012, these tumors were categorized as: 1- neuroendocrine tumor, well-differentiated; 2- neuroendocrine carcinoma, poorly differentiated/small cell carcinoma; and 3- invasive breast carcinoma with neuroendocrine differentiation. In this study, we reviewed NEBC except poorly differentiated/small cell carcinoma variant in order to define the morphological growth patterns and cytonuclear details of these tumors. All breast surgical excision materials between 2007 and 2016 were re-evaluated in terms of neuroendocrine differentiation. Thirty-six cases showing positive staining for synaptophysin and/or chromogranin A in ≥50% of tumor cells were included in the study. All cases were female with a mean age of 67.4. Mean tumor diameter was 26 mm. Multifocality was noted in 5 cases. Grossly, they were mostly infiltrative mass lesions. T stages, identified in 34 cases, were as follows: 13 cases with pT1; 19 pT2 and 2 pT3. We described schematically 4 types of patterns depending on predominant growth pattern, except one case: 1) Large-sized solid cohesive groups (6 cases), 2) Small- to medium-sized solid cohesive groups with trabeculae/ribbons and glandular structures (6 cases), 3) Mixed growth patterns (20 cases), 4) Invasive tumor with prominent extracellular and/or intracellular mucin (3 cases). The tumor cells were mostly polygonal-oval with eosinophilic/eosinophilic-granular cytoplasm. The nuclei of tumor cells were mostly round to oval with evenly distributed chromatin. Only 5 cases showed high grade nuclear and histological features. Molecular subtypes of the cases were as follows: 33 luminal A, 2 luminal B, and 1 triple negative. NEBC should come to mind when a tumor display one of the morphological patterns described above, composed of monotonous cells with mild to moderate nuclear pleomorphism and abundant eosinophilic/eosinophilic granular or clear cytoplasm, especially in elderly patients.