Immunohistochemical evaluation of osteopontin expression in triple-negative breast cancer.

Introduction: Triple-negative breast cancer (TNBC) is associated with lack of expression of estrogen and progesterone receptors and HER2 and is the subgroup of breast cancers with the worst prognosis. Osteopontin is a phosphorylated glycoprotein whose overexpression may occur in pathological states such as cancers. The main purpose of our study was to evaluate the immunohistochemical expression of osteopontin in connection with the analysis of recognized clinical and pathological prognostic factors in primary sites of TNBC with and without lymph node metastases. Material and methods: The immunohistochemical evaluation of osteopontin expression in 35 women with TNBC, chosen from a group of 726 patients, was performed. The material came from the excisional biopsies of primary breast cancers and total mastectomies. Results: All patients showed expression of osteopontin, in most cases the expression of osteopontin rated at [+] (57.1%) and [++] (42.9%). Our study analyzed the relationship between the expression of osteopontin and traditional prognostic markers, such as the tumor grade, size, and lymph node involvement. We found a strong relationship only between the expression of osteopontin and the presence of lymph node metastases (p ≤ 0.0001). 93% of patients for whom the expression of osteopontin was determined at [++] had metastasis to lymph nodes and, for comparison, only 15% of women for whom the expression of osteopontin was rated at [+] showed the presence of metastases in the lymphatic nodes. Conclusions: There is a correlation between osteopontin expression and the presence of lymph node metastases in TNBC, suggesting that osteopontin plays an important role in the invasiveness of TNBC.

Cancer-associated inflammation: pathophysiology and clinical significance.

PURPOSE: Cancer cells, despite stemming from the own cells of their host, usually elicit an immune response. This response usually enables elimination of cancer at its earliest stages. However, some tumors develop mechanisms of escaping immune destruction and even profiting from tumor-derived inflammation. METHODS: We summarized the roles of different immune cell populations in various processes associated with cancer progression and possible methods of reshaping tumor-associated inflammation to increase the efficacy of cancer therapy. RESULTS: Changes in various signaling pathways result in attraction of immunosuppressive, pro-tumorigenic cells, such as myeloid-derived suppressor cells, tumor-associated macrophages, and neutrophils, while at the same time suppressing the activity of lymphocytes, which have the potential of destroying cancer cells. These changes promote tumor progression by increasing angiogenesis and growth, accelerating metastasis, and impairing drug delivery to the tumor site. CONCLUSION: Due to its multi-faceted role in cancer, tumor-associated inflammation can serve as a valuable therapy target. By increasing it, whether through decreasing overall immunosuppression with immune checkpoint inhibitor therapy or through more specific methods, such as cancer vaccines, oncolytic viruses, or chimeric antigen receptor T cells, cancer-derived immunosuppression can be overcome, resulting in immune system destroying cancer cells. Even changes occurring in the microbiota can influence the shape of antitumor response, which could provide new attractive diagnostic or therapeutic methods. Interestingly, also decreasing the distorted tumor-associated inflammation with non-steroidal anti-inflammatory drugs can lead to positive outcomes.

Current State of Knowledge on the Immune Checkpoint Inhibitors in Triple-Negative Breast Cancer Treatment: Approaches, Efficacy, and Challenges.

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype with limited treatment options. Recently, there has been a growing interest in immunotherapy with immune checkpoint inhibitors (ICIs) in TNBC, leading to extensive preclinical and clinical research. This review summarizes the current state of knowledge on ICIs efficacy and their predictive markers in TNBC and highlights the areas where the data are still limited. Currently, the only approved ICI-based regimen for TNBC is pembrolizumab with chemotherapy. Its advantage over chemotherapy alone was confirmed for non-metastatic TNBC regardless of programmed death-ligand 1 (PD-L1) expression (KEYNOTE-522) and for metastatic, PD-L1-positive TNBC (KEYNOTE-355). Pembrolizumab's efficacy was also evaluated in monotherapy, or in combination with niraparib and radiation therapy, showing potential efficacy and acceptable safety profile in phase 2 clinical trials. Atezolizumab + nab-paclitaxel increased the overall survival (OS) over placebo + nab-paclitaxel in early TNBC, regardless of PD-L1 status (IMpassion031). In IMpassion130 (untreated, advanced TNBC), the OS improvement was not statistically significant in the intention-to-treat population but clinically meaningful in the PD-L1 positive cohort. The durvalumab-anthracycline combination showed an increased response durability over placebo anthracycline in early TNBC (GeparNuevo). Several phase 1 clinical trials also showed a potential efficacy of atezolizumab and avelumab monotherapy in metastatic TNBC. ICIs appear to be applicable in both neoadjuvant and adjuvant settings, and are both pretreated and previously untreated patients. Further research is necessary to determine the most beneficial drug combinations and optimize patient selection. It is essential to identify the predictive markers for ICIs and factors affecting their expression.

Medullary breast cancer is a predominantly triple-negative breast cancer - histopathological analysis and comparison with invasive ductal breast cancer.

Introduction: Medullary breast cancer (MdBC) is an uncommon type of breast cancer representing 1-7% of all cases. It is characterized by the occurrence of many histopathological features associated with a high grade of malignancy. Material and methods: Twelve MdBCs chosen from a group of 1,122 women suffering from invasive breast cancer were analyzed. Histopathological examination and analysis of a basic molecular profile, i.e. estrogen (ER), progesterone (PR) and HER2 receptor expression, and their comparison with invasive ductal breast cancer (IDC), were performed. Results: MdBC accounted for 1.07% of all analyzed invasive breast cancer patients. All patients were female, with an average age of 58.54 years. The MdBC group exhibited a larger median tumor diameter (2.05 vs. 1.89 cm), although ≥ T2 tumors comprised 42% vs. 51% for IDCs. Women without regional lymph node involvement (pN0) (83%) formed the largest group. There was a statistically significant difference in the presence of nodal involvement between the studied groups (p < 0.001). Based on the histological grade of malignancy, the majority of MdBC comprised grade II tumors (G2) (93%). In general, MdBC showed statistically higher histologic grade (G1-G3) than IDC (p = 0.003). The 5-year overall survival rate of MdBC patients was 91%. Most MdBCs (92%) were triple-negative, whereas the remaining 8% were HER2 positive. Conclusions: MdBC presented at a younger age than IDC, had a higher histological grade, larger median size and less frequent regional lymph node involvement. Most MdBCs were triple-negative, whereas IDCs were predominantly luminal. Despite numerous aggressive pathological features of MdBC, its clinical outcome and overall prognosis are favorable.

Pulmonary blastoma in a pregnant woman: a case report and brief review of the literature.

BACKGROUND: Pulmonary blastoma (PB) comprises a rare heterogeneous group of lung tumours typically containing immature epithelial and mesenchymal structures that imitate the embryonic lung tissue and extremely rarely occurs during pregnancy. Although cough and haemoptysis are the most common PB symptoms, they usually indicate other serious pregnancy-related complications. CASE PRESENTATION: The article presents the unusual case of a 22-year-old pregnant woman diagnosed with PB during pregnancy. CONCLUSIONS: PB is characterized by poor prognosis and patients' outcome relies on a rapid diagnosis. Surgery remains the most common and effective treatment. Due to the extreme rarity, the literature contains only single mentions of PB in pregnancy, thus its impact on the course of pregnancy and the developing fetus remains unknown.

Carbon footprint of inhalers in COPD therapy in 2018 and 2019 in Poland in response to the Kigali amendment.

The treatment of patients with obstructive airway diseases is based on the use of inhalation preparations. Some of them, mainly including pressurized metered dose inhalers (pMDIs), contain compressed gases - hydrofluoroalkanes, which generate carbon dioxide emissions, creating the so-called carbon footprint. AIM: The aim of the study was to evaluate the consumption of individual active substances, the types of inhalers used and calculation of the carbon footprint of popular therapies in 2018 and 2019 in Poland. MATERIALS AND METHODS: The ratio of pMDI vs DPI (dry powder inhaler) data and the data on using long-acting ß2-agonists (LABAs), shortacting muscarinic antagonists (SAMAs), long-acting muscarinic antagonists (LAMAs), LAMA+LABAs, LAMA+LABA+ICSs (inhaled corticosteroids) on Polish market during 2018 and 2019 were analyzed. The carbon footprint of such therapies was counted. Then, we studied the reduction of the carbon footprint for scenario A (reducing pMDI by 50%) and scenario B (reducing pMDI by 80%) in the following steps of analysis. RESULTS: The general structure of pMDI/DPI in Poland in COPD area was not changed in 2019 vs 2018. The carbon footprint is primarily created by pMDI SAMAs. In 2019 in Poland pMDI SAMAs were 1.6 mio units (the same as in 2018), which generated 33.5 kt CO2e annually, but the whole category generates 40.8 kt CO2e. Scenario A gives us a benefit of 18.8 kt CO2e reduction and scenario B brings us a benefit of 29.9 kt CO2e reduction of emissions. CONCLUSIONS: Despite Poland's ratification the Kigali amendment did not affect pMDI consumption and did not reduce the carbon footprint. The lower carbon footprint of DPIs should be considered alongside other factors when choosing inhalation devices.

Assessment of Pain, Acceptance of Illness, Adjustment to Life, and Strategies of Coping with Illness among Patients with Gastric Cancer.

Gastric cancer is the fourth leading cause of deaths in Poland. The standard treatment for non-advanced gastric cancer is surgery, which significantly reduces the quality of life of patients. The objective of the study was to evaluate the strategy of coping with pain and its control, acceptance of illness, and adjustment to living with cancer in patients suffering from gastric cancer. The analysis of the impact of socio-economic factors on the above-mentioned problems was also analyzed. The study was conducted among 93 patients diagnosed with gastric cancer, treated on an outpatient basis at the Oncology Center-Maria Sklodowska-Curie Institute in Warsaw in 2017-2018. The PAPI (paper and pencil interview) technique was used. The questionnaire interview included metric questions (socio-economic variables) and four psychometric tests: BPCQ (the Beliefs about Pain Control Questionnaire), CSQ (the Pain Coping Strategies Questionnaire), AIS (Acceptance of Illness Scale), and Mini-MAC (Mental Adjustment to Cancer) test. In the area of pain control, patients with gastric cancer assign the greatest role to internal factors (M = 16.34, SD = 4.93), although women obtained the highest value in the impact of physicians. In the area of coping with pain, patients most likely select the strategy of praying/hoping (M = 22.19, SD = 9.36). The mean value of acceptance of illness for patients with gastric cancer is M = 24.02, SD = 7.69, and it is not conditioned by any socio-economic variable. In the area of mental adjustment to illness, the highest values were obtained by positive reevaluation (M = 20.73, SD = 3.35) and fighting spirit (M = 20.68, SD = 3.98). Patients with gastric cancer control pain mainly through internal factors. The most frequently chosen strategy for coping with pain is praying/hoping, and positive reevaluation prevails in the field of mental adjustment. The results point to specific factors that can affect the patient's pain, quality of life, and treatment outcomes. Knowing the diversity of these factors, it is possible to plan specific psychotherapeutic activities for specific groups of people that could be a supplement to the standard treatment process.

Clinicopathological factors associated with novel prognostic markers for patients with triple negative breast cancer.

INTRODUCTION: Triple negative breast cancer (TNBC) is characterized by a worse prognosis than other breast cancer subtypes. TNBC is defined by lack of expression of estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2. The aim of this analysis was to evaluate the relationship between immunohistochemical expression of novel prognostic markers (erythropoietin (EPO) and erythropoietin receptor (EPO-R)) and clinicopathological features of TNBC and non-TNBC patients. MATERIAL AND METHODS: Our analysis was conducted on a group of 162 patients with breast carcinoma with lymph node metastasis (111 TNBC and 51 non-TNBC). All statistical analyses were performed with SPSS software v 12.0. RESULTS: Histopathologic subtyping of the 111 triple negative breast cancers identified 89.1% invasive ductal carcinomas of no special type and 10.9% other special types of cancers. TNBC more often presented EPO-R and EPO expression (36%; 37.8%) than non-TNBC (23.5%; 29.4%). Non-TNBC subgroup showed statistically significant correlation only between Ki-67 expression and histological grade (G1-G3) (p < 0.001), while TNBC subgroup demonstrated significant correlation between Ki-67 expression and histological grade (G1-G3) and tumor size (pT1-pT4) as well (p = 0.002; p = 0.042), between the EPO-R expression and histological grade (G1-G3) (p < 0.001). CONCLUSIONS: The relationship between the expression of EPO-R and histological malignancy grade in triple negative breast cancer, suggests that the present EPO-R expression in TNBC may constitute an additional prognostic factor.

Expression of multidrug resistance protein P-glycoprotein in correlation with markers of hypoxia (HIF-1α, EPO, EPO-R) in invasive breast cancer with metastasis to lymph nodes.

INTRODUCTION: Overexpression of the mdr-1 gene is the earliest discovered mechanism of multidrug resistance, which is associated with P-glycoprotein (P-gp) - a cell membrane protein responsible for the efflux of drugs of various structures out of cancer cells. Although the expression of P-glycoprotein has been demonstrated in many cancer types, its relation to markers of hypoxia such as HIF-1α, EPO-R or EPO in invasive breast cancer is not well established. The aim of this research was to analyze the co-expression of P-glycoprotein and the markers of tissue hypoxia HIF-1α, EPO, and EPO-R by immunohistochemistry in invasive breast cancer classified according to the presence of steroid receptors and the HER2 receptors. MATERIAL AND METHODS: Tissue samples were collected from 58 patients with the diagnosis of invasive breast cancer with lymph node metastases. The expression of P-gp, HIF-1α, EPO-R and EPO was determined by immunohistochemistry. RESULTS: Of all the invasive breast cancers with lymph node metastases, 15.5% expressed P-gp in cell membrane and tumor blood vessels. In our research, there was a significant positive correlation between HER2-positive tumors that did not express steroid receptors (ER-/PR-/HER2+), and P-gp expression (p = 0.049, r = 0.105). Moreover, there was a significant positive correlation between EPO expression and P-gp (p < 0.001, r = 0.474), and between HIF-1α expression and P-gp (p = 0.00475, r = 0.371). CONCLUSIONS: We found that HIF-1α and EPO expression is significantly associated with P-gp expression in invasive breast cancer with lymph node metastases. An important result of our study is the demonstration of a correlation between P-gp expression and patients with HER2-positive breast tumors that do not express steroid receptors.

Retrospective evaluation of histopathological examinations in invasive ductal breast cancer of no special type: an analysis of 691 patients.

INTRODUCTION: Invasive ductal carcinoma (IDC) is the most common type of breast cancer in women and accounts for about 80% of all breast cancers. MATERIAL AND METHODS: The material consisted of histological preparations derived from 691 patients treated for IDC-NST. RESULTS: In our own study material, invasive ductal breast cancer of no special type accounted for more than 60% of cases, with the largest percentage of tumors being classified as G2 (53.96%) and G3 (28.98%). In terms of tumor size, the most common IDC-NST tumors were those of stage T1c (34.59%) and T2 (35.31%). The incidence of lymph node involvement was also assessed to reveal that no lymph node metastases were present in 45.44% of IDC-NST tumors. In the histopathological analysis of IDC-NST, significant statistical correlation was demonstrated between the presence of lymph node metastases and the histological malignancy grade (N0/G1-G3 p = 0.0103; N1A/G1-G3 p = 0.0498; N1B/G1-G3 p< 0.001; N3/G1-G3 p = 0.0027; N4/G1-G3 p < 0.001), between the presence of lymph node metastases and the tumor size (N0/T1-T4 p = 0.00295; N1B/T1-T4 p < 0.001; N2/T1-T4 p < 0.001; N2A/T1-T2 p < 0.001; N4/T1-T4 p < 0.001; Nx/T1-T4 p = 0.0447), as well as between the histological malignancy grade and the tumor size (G1/T1-T4 p < 0.001; G1/2/T1-T4 p < 0.001; G2/3/T1-T4 p < 0.0267). CONCLUSIONS: Own research demonstrated that the most common histological type of breast cancer is invasive ductal carcinoma of no special type (IDC-NST); statistically significant correlations were demonstrated in IDC-NST patients between the lymph node involvement status and the histological malignancy grade or tumor size as well as between the histological malignancy grade and the tumor size.

Selected tumor markers in the routine diagnosis of chromophobe renal cell carcinoma.

Renal cell carcinoma is one of the most malignant tumors, affecting men more frequently than women and constituting nearly 90% of all kidney tumors. Chromophobe renal cell carcinoma has been described as a new histological type of renal cell carcinoma. Chromophobe renal cell carcinoma constitutes up to 5% of all cases of kidney cancer. It is characterized by a significant number of deletions in many chromosomes, as well as the loss of entire chromosomes. Chromophobe renal cell carcinoma arises from tubular cells or cells of the macula densa. In contrast to other types of kidney cancer, it occurs with equal frequency in men and women, mostly in the sixth decade of life. It is characterized by a relatively good prognosis and exhibits a low degree of malignancy. Histopathologic diagnosis of ChRCC can be a diagnostic challenge because these tumors may resemble oncocytoma or conventional cancer. Research by Mathers et al. proposed the use of cytokeratin 7 as a marker useful in the differentiation of these changes.

Immunohistochemical characteristics of basal-like breast cancer.

Basal-like breast cancer (BLBC) occurs mainly in young patients. It is characterized by an aggressive clinical outcome, presence of distant metastases, particularly within the first five years of the disease, bad prognosis and relatively high mortality. Recently greater interest of scientists in this subtype of breast cancer has been observed. Despite such many well-known potential biomarkers of BLBC, currently there is no official international panel of antigens dedicated to diagnosis of this subtype of breast cancer. The most commonly used set in this case contains four antibodies - estrogen receptor (ER), epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) and cytokeratins (CK) 5/6 - although it cannot provide one hundred percent detectability of these lesions. Incorporation of additional biomarkers into a panel can increase specificity, at the potential cost of sensitivity. Many biomarkers have been associated with the basal-like phenotype, and those with high sensitivity and/or specificity could improve the performance of immunohistochemical surrogate panels. Work on detection of the best of them is constantly being performed.

The role of oestrogen and progesterone receptors in breast cancer - immunohistochemical evaluation of oestrogen and progesterone receptor expression in invasive breast cancer in women.

AIM OF THE STUDY: Expression of oestrogen and progesterone receptors is a very powerful and useful predictor. Because the response rate to hormonal treatment in breast cancer is associated with the presence of oestrogen and progesterone receptors, assessment of the receptor expression profile allows for prediction of breast cancer response to hormonal treatment. The aim of this study was to assess whether the expression of receptors for oestrogen (ER) and progesterone (PR) in the tumour tissue of patients with invasive breast cancer correlated with tumour histological type, histological grade of malignancy, tumour size, and lymph node status. MATERIAL AND METHODS: Materials consisted of histological preparations derived from patients treated for invasive breast cancer. Evaluations were conducted with histopathological and immunohistochemical methods using suitable antibodies. RESULTS: Among 231 cases of breast cancer 18 invasive lobular carcinomas (ILC) and 213 invasive ductal carcinomas (IDC) were diagnosed. Taking the histological type of tumour into account, oestrogen receptor-positive reaction was observed in 74.2% of IDC and 77.8% of ILC, and the positive response to PR was observed in 67.1% of IDC and 61.1% of ILC. Considering the histological grade, ER- in the largest percentage (72%) was observed in second-grade (G2) invasive carcinomas. Similarly, PR expression (75%) was found in the largest percentage in second-grade (G2) carcinomas. Based on our own studies and data from literature, it appears that the ER (+) status is an indicator of good prognosis, because it points to a less aggressive cancer, in which overall survival and disease-free time is longer in comparison with ER (-) tumours. CONCLUSIONS: Determination of ER status may, therefore, have significant clinical value and is widely used in routine pathological diagnostics.

Immunohistochemical evaluation of human epidermal growth factor receptor 2 and estrogen and progesterone receptors in invasive breast cancer in women.

INTRODUCTION: Estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2) expression are crucial in the biology of breast carcinoma. HER-2/neu gene is amplified and overexpressed in 15-30% of invasive breast cancers. HER-2-positive breast cancers have worse prognosis than HER-2 negative tumors and possess distinctive clinical features. The aim of this study was to assess the expression of HER2 in cancer tissue of patients with invasive breast cancer in correlation with tumor type, histological grade, tumor size, lymph node status, and expression of estrogen receptor and progesterone receptor. MATERIAL AND METHODS: Formalin-fixed, paraffin-embedded tissues from 40 patients with invasive HER-2-positive breast cancer and from 191 patients with HER-2-negative breast cancer were used in this study. HER2 expression was determined using the test HerceptTest™ DAKO. RESULTS: Among 231 cases of breast cancer, 18 invasive lobular carcinomas and 213 invasive ductal carcinomas were diagnosed. Sixty percent of HER-2-positive breast cancers were ER-positive compared with 77% in the HER-2-negative group (p = 0.002). The expression of PR was observed in 43% of HER-2-positive breast cancers and in 72% of HER2-negative tumors (p = 0.003). Excessive expression of HER2 protein was detected in 60% of patients positive for estrogen receptors, which may worsen prognosis in these patients. CONCLUSIONS: Determination of HER2 overexpression in breast cancer patients, allows for a determination of a group of patients with a worse prognosis.