Clinicopathological significance of the immunologic signature (PDL1, FOXP3+ Tregs, TILs) in early stage triple-negative breast cancer treated with neoadjuvant chemotherapy.

Patients with breast cancer are appropriate candidates for neoadjuvant chemotherapy (NAC) to facilitate conservative surgery. The chemotherapeutic agents may exert their action by inducing the anti-tumor immune response. This study aimed to evaluate the tumor immune microenvironment including PD-L1, Foxp3+ Tregs, and TILs count in early stages TNBC patients (stage T1, T2) before and after neoadjuvant chemotherapy and their correlation with the clinical and pathological response. Fifty patients of TNBC patients were enrolled in this study; all of them received neoadjuvant chemotherapy. TILs count, Foxp3+ Tregs, and PD-L1 immunohistochemical expression were investigated in all cases before NAC and then evaluated in residual masses after surgery. Data on the clinical and pathological response to NAC were collected and then statistically analyzed. PDL1 expression was detected in 24% of all studied cases, all of them were node-positive (P < 0.002); while Foxp3+ Tregs expressed in 50% and high TILs in 28%. Pathological complete response (pCR) was achieved in 40% of patients and was associated with high TILs expression (P < 0.02) and absence of Foxp3+ Tregs and PDL1 (P < 0.001 for each). In conclusion, Pathologic complete response to NAC was associated with the immunological profile of TNBC. High TILs expression with concomitant decreased PD-L1 expression and low FOXP3+ Tregs is associated with favorable tumor prognosis. Combined therapeutic approaches aiming to PD-L1 block and Tregs depletion might improve treatment efficacy in TNBC.

Prognostic impact of EGFR and cytokeratin 5/6 immunohistochemical expression in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) has an aggressive behavior and limited therapeutic options due to lack of targeted therapy. We aimed in this study to assess the immunohistochemical expression of EGFR and cytokeratin 5/6 and their ability to predict survival and response to neoadjuvant chemotherapy (NAC) among triple-negative breast cancer patients. Thirty-five cases with TNBC were studied by immunohistochemistry for EGFR and CK5/6 expression. Data on overall survival (OS), disease-free survival (DFS) and response to NAC were collected. The resulted data were statistically analyzed. Invasive carcinoma of no special type (NST) was the predominant histopathological type (80%). The commonest histological grade was grade II-III (88.6%). About 57.1% of TNBC cases were CK5/6-positive, and 71.4% were EGFR-positive. EGFR expression showed a significant association with tumor grade and axillary lymph node metastasis (p=0.006, 0.016 respectively). EGFR expression was related to unfavorable response to NAC (p=0.036), poor OS (p=0.002) and poor DFS (p=0.003). CK5/6 expression showed a significant association with tumor grade, unfavorable response to NAC, poor OS & DFS (p=0.007, 0.048, <0.001, 0.043 respectively). Immunohistochemical expression of EGFR and/or CK5/6 showed a high significant association with an unfavorable response to NAC, poor DFS &OS (p=0.010, 0.012, 0.030 respectively). CONCLUSIONS: EGFR and CK5/6 are adverse prognostic markers in TNBC. EGFR and CK5/6 expression could serve as biomarkers for identifying TNBC patients with poor survival that are unlikely to benefit from neoadjuvant chemotherapy. So, targeted therapy against EGFR may be a hopeful therapy for TNBC with NAC resistance.

Prognostic Impact of FSTL3, ADAM12, and FAT4 in Patients of Colon Cancer: Clinicopathologic Study.

There is a cellular crosstalk between Wnt/ß-catenin and Hippo/Yes-related protein 1 signaling paths in colon cancer (CC) which promotes EMT processes that mediate the metastatic progression of CC. We aimed to evaluate follistatin-like 3 (FSTL3), ADAM12, and FAT4 expressions in CC. A statistical analysis was done to establish how disease-free survival, overall survival (OS), and relapse all performed a prognostic role. High FSTL3 was detected in 68% of CC and significantly related to left-sided tumors ( P = 0.002) and the advanced tumor features, such as metastasis ( P = 0.010), pT ( P = 0.006), high grade ( P = 0.005), lymph node contribution ( P = 0.013), and advanced stage ( P = 0.003). Positive ADAM12 expression was observed in 60% and significantly related to left-sided tumors ( P = 0.001) and significantly common in high grade ( P = 0.028), lymph node involvement ( P < 0.001), and advanced stage ( P = 0.004). Low FAT4 expression was recognized in 76% and linked with the right-sided tumors ( P = 0.036). FAT4 expression was contrariwise linked with CC grade ( P < 0.001). Furthermore, FAT4 expression was inversely correlated with lymph node involvement ( P = 0.002), metastasis ( P = 0.046), and advanced stage ( P = 0.002). During the follow-up, 14 cases were relapsed and positively associated with high FSTL3 expression ( P = 0.001) and ADAM12 expression ( P < 0.001), but negatively linked with FAT4 expression ( P = 0.003). Shorter disease-free survival was substantially correlated with positive ADAM12, extreme FSTL3, and low FAT4 expression ( P < 0.001, P = 0.002, P = 0.003, consecutively). Moreover, Kaplan-Meier curves demonstrated a significant correlation between shorter OS with extreme FSTL3, positive ADAM12, and low FAT4 ( P = 0.004, <0.001, 0.019, consecutively). High FSTL3, positive ADAM12, and low FAT4 expression are unfavorable prognostic influences in CC that may be accountable for relapse and therapeutic resistance in CC.

A prospective multicentre study evaluating the outcomes of the abdominal wall dehiscence repair using posterior component separation with transversus abdominis muscle release reinforced by a retro-muscular mesh: filling a step.

BACKGROUND: This study aimed to evaluate the results of posterior component separation (CS) and transversus abdominis muscle release (TAR) with retro-muscular mesh reinforcement in patients with primary abdominal wall dehiscence (AWD). The secondary aims were to detect the incidence of postoperative surgical site occurrence and risk factors of incisional hernia (IH) development following AWD repair with posterior CS with TAR reinforced by retromuscular mesh. METHODS: Between June 2014 and April 2018, 202 patients with grade IA primary AWD (Björck's first classification) following midline laparotomies were treated using posterior CS with TAR release reinforced by a retro-muscular mesh in a prospective multicenter cohort study. RESULTS: The mean age was 42 ± 10 years, with female predominance (59.9%). The mean time from index surgery (midline laparotomy) to primary AWD was 7 ± 3 days. The mean vertical length of primary AWD was 16 ± 2 cm. The median time from primary AWD occurrence to posterior CS + TAR surgery was 3 ± 1 days. The mean operative time of posterior CS + TAR was 95 ± 12 min. No recurrent AWD occurred. Surgical site infections (SSI), seroma, hematoma, IH, and infected mesh occurred in 7.9%, 12.4%, 2%, 8.9%, and 3%, respectively. Mortality was reported in 2.5%. Old age, male gender, smoking, albumin level < 3.5 gm%, time from AWD to posterior CS + TAR surgery, SSI, ileus, and infected mesh were significantly higher in IH. IH rate was 0.5% and 8.9% at two and three years, respectively. In multivariate logistic regression analyses, the predictors of IH were time from AWD till posterior CS + TAR surgical intervention, ileus, SSI, and infected mesh. CONCLUSION: Posterior CS with TAR reinforced by retro-muscular mesh insertion resulted in no AWD recurrence, low IH rates, and low mortality of 2.5%. Trial registration Clinical trial: NCT05278117.

Recurrent appendicitis following successful drainage of appendicular abscess in adult without interval appendectomy during COVID-19. Prospective cohort study.

BACKGROUND: COVID-19 infection is a global pandemic that affected routine health services and made patients fear to consult for medical health problems, even acute abdominal pain. Subsequently, the incidence of complicated appendicitis increased during the Covid-19 pandemic. This study aimed to evaluate recurrent appendicitis after successful drainage of appendicular abscess during COVID-19. MATERIAL AND METHODS: A prospective cohort study conducted in the surgical emergency units of our Universities' Hospitals between March 15, 2020 to August 15, 2020 including patients who were admitted with the diagnosis of an appendicular abscess and who underwent open or radiological drainage. Main outcomes included incidence, severity, and risk factors of recurrent appendicitis in patients without interval appendectomy. RESULTS: A total of 316 patients were included for analysis. The mean age of the patients was 37 years (SD ± 13). About two-thirds of patients were males (60.1%). More than one-third (39.6%) had co-morbidities; type 2 diabetes mellitus (T2DM) (22.5%) and hypertension (17.1%) were the most frequent. Approximately one quarter (25.6%) had confirmed COVID 19 infection. About one-third of the patients (30.4%) had recurrent appendicitis. More than half of them (56.3%) showed recurrence after three months, and 43.8% of patients showed recurrence in the first three months. The most frequent grade was grade I (63.5%). Most patients (77.1%) underwent open surgery. Age, T2DM, hypertension, COVID-19 infection and abscess size >3 cm were significantly risking predictors for recurrent appendicitis. CONCLUSIONS: Interval appendectomy is suggested to prevent 56.3% of recurrent appendicitis that occurs after 3 months. We recommend performing interval appendectomy in older age, people with diabetes, COVID-19 infected, and abscesses more than 3 cm in diameter. RESEARCH QUESTION: Is interval appendectomy preventing a high incidence of recurrent appendicitis after successful drainage of appendicular abscess during COVID-19 pandemic?

Clinicopathological Features and Treatment Challenges in Triple Negative Breast Cancer Patients: A Retrospective Cohort Study.

OBJECTIVE: As the genetic and molecular profiles of triple negative breast carcinoma (TNBC) are elucidated, multiple therapeutic targets have been produced. TNBC with less than 1% androgen receptor (AR) expression may respond to enzalutamide with greater response association in higher levels. A metronomic dose of capecitabine and docetaxel are effective developed drugs for angiogenic process inhibition. We aimed to demonstrate the treatment outcome of triple-negative breast cancer patients in correlation to their clinicopathological features. MATERIALS AND METHODS: A retrospective cohort study of 80 TNBC patients was conducted. The patients underwent proper observation with the reporting of their treatment and follow-up data. Patients with a metastatic disease, neoadjuvant chemotherapy, follow-up drop or data shortage were excluded from the survival analysis. RESULTS: The study results revealed a significant association between negative androgen expression and younger age ≤35 years, premenopausal status, higher grade, extracapsular extension, lymphovascular invasion, Ki 67, and CA15-3 (p=0.003, 0.02, < 0.001, 0.001, 0.027, 0.005, 0.009 respectively). The three-year overall survival (OS) in patients who received bicalutamide was better than those patients who received capecitabine or docetaxel but of no significance (p=0.46). The three-year disease free survival (DFS) was significantly better in the bicalutamide arm versus the other two groups (p=0.012). CONCLUSIONS: We concluded that extended adjuvant antiandrogen such as bicalutamide and metronomic capecitabine are well tolerated with accepted compliance and affordability compared to docetaxel and are warranted for problem-solving and better DFS and OS in some TNBC patients.

Evaluation of axillary reverse mapping (ARM) in clinically axillary node negative breast cancer patients - Randomised controlled trial.

BACKGROUND: Axillary lymph node dissection (ALND) is an important procedure for control of axillary nodal metastasis in breast cancer patients. Lymphedema, restriction of shoulder movement and axillary nodal recurrence are the most disabling complications of the procedure. Axillary reverse mapping (ARM) procedure for arm lymph node identification emerged as a step for their preservation during ALND. Here we are testing the effect of ARM on lymphedema development and whether it compromises oncological safety in early breast cancer patients. PATIENTS AND METHODS: 98 clinically node free breast cancer female patients undergoing completion ALND after positive sentinel lymph node biopsy were recruited in the study. They were put into group A (49 patients with ARM + ve preservation ALND) and group B (49 patients in the conventional ALND group). ARM procedure was performed in both groups, ARM positive nodes were preserved in group A, marked and taken out with other axillary LN in group B. The outcome was histopathology of ARM + ve LN, development of arm lymphedema, and restriction of shoulder movement on follow-up. RESULTS: ARM was positive in 46 patients (93.8%) in group A and 43 patients (87.8%) in group B, ARM + ve LN revealed positive metastasis only in 1 patient (2.3%) in group B. Lymphedema developed in 3 (6.5% patients in group A and 9 patients (20.9%) in group B. Restriction of shoulder movement showed a non-significant difference between the two groups. CONCLUSION: Axillary reverse mapping and preservation of arm lymphatics helped to decrease the lymphedema rate without compromising oncological safety in early breast cancer.

Changing the innate consensus about mesh fixation in trans-abdominal preperitoneal laparoscopic inguinal hernioplasty in adults: Short and long term outcome. Randomized controlled clinical trial.

INTRODUCTION: Inguinal hernioplasty is the standard treatment for inguinal hernia in adults. Mesh fixation was used to keep mesh in place for which various mesh fixation techniques have been used in laparoscopic inguinal hernia repair in adults, but their effectiveness has remained inconclusive. AIM OF THE WORK: to evaluate non fixation method of mesh laparoscopic inguinal hernioplasty as safe and effective as regard short and long term outcomes. PATIENTS AND METHODS: Over the period from July 2013 to July 2018, 798 patients with oblique inguinal hernias undergoing Trans abdominal preperitoneal technique (TAPP) were randomized into 3 groups: Group A; mesh non fixation 266 patients. Group B; tacker mesh fixation 266 patients Group C: Cyanoacrylic tissue glues (Histoacryl) mesh fixation 266 patients. Clinical effects were assessed by the following variables: intraoperative data, postoperative outcome as regard recurrence rate, postoperative pain [on visual analogue score (VAS)], analgesic consumption, operation time, hospital stay, and patient costs. Follow up was 18 months. RESULTS: There was no statistical difference between groups (A) and Group (C) regarding operative time, postoperative complications, and length of hospital stay and risk of chronic groin pain, postoperative pain score. In Group (B): the postoperative pain and complications were higher. There were 5 cases of hernia recurrence in all groups, but no significant differences among the three groups. CONCLUSION: Tacker Mesh fixation increased the risk of chronic groin pain. Pain score was higher with tacker mesh fixation. Laparoscopic TAPP inguinal hernia repair without tacker mesh fixation was safe and feasible with no significant increase in recurrence rates. Furthermore, mesh fixation with tacker procedure increased the risk of postoperative complications and patient costs. All ethical approval was given by our Faculty of Medicine medical ethical committee.

Prognostic Value of Cyclin D1 and CD44 Expression in Gastric Adenocarcinoma.

BACKGROUND: Worldwide, gastric carcinoma (GC) is the 5th most common malignancies in both sexes representing 6.8% of the total fatalities and is the 3rd leading cause of cancer death representing 8.8% of total fatalities. In Egypt, GC considers the 12th leading cause of cancer death representing 2.2% of the total cancer mortality. A growing body of evidence supports that cancer stem cells (CSCs) are resistant to chemotherapy or radiation, and the cell adhesion molecule CD44 has been identified as a cell surface marker associated with cancer stem cell in several types of tumors including gastric cancer. CD44 regulates gastric stem cell proliferation by increasing cyclin D1 expression which represents an important regulatory protein in the cell cycle transition from G1 phase to S phase. This study aimed to investigate whether cyclin D1 and CD44 can be used as prognostic indicators in gastric cancer. MATERIAL AND METHODS: Forty formalin-fixed and paraffin-embedded gastric tissues, obtained from patients who underwent endoscopic resection or surgical resection, constituted the group of our study. The immunohistochemical expression of cyclin D1 and CD44 was examined and correlated with clinical-pathological parameters and outcome of the patients. RESULTS: Overexpression of CD44 and cyclin D1 was noted (in of 55 and 50% respectively). Cyclin D1 and CD44 positive expressions in GC were positively correlated with tumor differentiation (p = 0.020, p = 0.004 respectively), TNM stage (p < 0.001 for both), poor survival (p < 0.001 for both), and with increased rate of recurrence (p = 0.020, p = 0.005 respectively). CONCLUSION: CD44 and cyclin D1 were associated with poor prognosis in gastric cancer, and so, they comprise an attractive target for anticancer drug development.

C-MYC and BCL2: Correlation between Protein Over-Expression and Gene Translocation and Impact on Outcome in Diffuse Large B Cell Lymphoma

Background: Due to lack of availability of gene expression profiling (GEP) for most developing countries and clinicians; the immunohistochemistry (IHC) is mostly used in the clinical application. The aim of our study is to check the possibility of using IHC to detect MYC and BCL2 in our patients with diffuse large B-cell lymphoma (DLBCL) instead of GEP to stratify them into high and low-risk groups. This will help in a proper treatment choice of subsequent improvement in the survival outcome. Method: During the study period, 90 DLBCL patients were eligible. MYC and BCL2 evaluated by IHC and gene rearrangement by real-time PCR (RT-PCR) and correlated with clinical-pathological features and survival. Results: Through IHC, the expression of MYC, BCL2, and double expression was detected in 35.6%, 46.7% and 30% of patients, respectively. While by RT-PCR, it was 4.53±0.74 for MYC compared with 2.18±0.78 for BCL-2. Most patients with BCL2+/MYC+; double-expressor and double-hit lymphomas (DEL and DHL) had high stage (III, IV), more extra-nodal involvement, (P value <0.001) and intermediate to high International Prognostic Index (IPI) risk profile (P-value <0.001). The median overall survival was 14 months and 6 months for DEL and DHL, respectively. While all patients with DHL died during the follow-up period, the median PFS were only 2 months for DEL. There was a statistically significant correlation between mRNA of MYC and BCL2 with their protein expression (p<0.001). Conclusion: Our results confirmed the unique characters and poor outcome associated with DEL and DHL mandated the need for more intense therapy and not the standard protocol. Moreover, the significant correlation between protein overexpression and gene rearrangement may open the door for the possibility to use IHC instead of RT-PCR in developing countries.

Clinicopathological implications of genetic and immunohistochemical expression of S100A8, S100A9 and TLR5 in breast carcinoma / Implicaciones clinicopatológicas de la expresión genética e inmunohistoquímica de las expresiones S100A8, S100A9 y TLR5 en el carcinoma de mama

Introduction: Breast carcinoma (BC) is one of the most common cancer-related mortality among women worldwide. S100A9 and S100A8 are calcium-binding proteins involved in BC metastasis. Toll-like receptors (TLRs) are membrane-bound proteins that play a vital role in immune systems and carcinogenesis through inflammatory cytokines.Objectives: We aimed to evaluate of S100A8, S100A9 and TLR5 in breast carcinoma by IHC, their gene expression by PCR and investigate their correlation with clinicopathological characters and hormone status.Materials and methods: This study was done in Biochemistry & Molecular Biology and Pathology Departments, Zagazig University, Egypt. Biopsy was taken from 72 patients with invasive breast carcinoma cases admitted to Surgery Department, Zagazig University, between January 2018 and January 2021. 72 breast biopsies were obtained from adjacent normal breast (as a control). IHC, gene expression by q real-time PCR using S100A8, S100A9 and TRL5.Results: Positive S100A8, S100A9, TLR5 were 81.9%, 76.4%, 86.1% respectively with statistically significant association between advanced stage, presence of lymph node metastasis, ER.PR status and HER2 negative expression.Conclusiones: Based on our findings, we postulated that S100A8, S100A9, TLR5 play an important role in progression of BC and can be used as novel molecular targets for earlier BC detection and prediction for future therapies in breast carcinoma. (AU)

Introducción: El carcinoma de mama (BC, por sus siglas en inglés) es una de las muertes relacionadas con el cáncer más comunes entre las mujeres en todo el mundo. S100A9 y S100A8 son proteínas de unión al calcio implicadas en la metástasis del BC. Los receptores tipo peaje (TLR, por sus siglas en inglés) son proteínas unidas por membrana que juegan un papel vital en los sistemas inmunitarios y carcinogénesis a través de citocinas inflamatorias.Objetivos: Evaluar S100A8, S100A9 y TLR5 en el BC por IHC, su expresión génica por PCR e investigar su correlación con los caracteres clínico patológicos y el estado hormonal.Material y métodos: Este estudio se realizó en los Departamentos de Bioquímica y Biología Molecular y Patología de la Universidad de Zagazig, Egipto. Se tomó biopsia de 72 pacientes con carcinoma de mama invasivo ingresados en el Departamento de Cirugía de la Universidad de Zagazig, entre enero de 2018 y enero de 2021. Setenta y dos biopsias de mama se obtuvieron de mama normal adyacente (como control). IHC, expresión génica por q PCR en tiempo real usando S100A8, S100A9 y TRL5.Resultados: Positivo S100A8, S100A9 y TLR5 fueron del 81,9, 76,4 y 86,1%, respectivamente, con asociación estadísticamente significativa entre el estadio avanzado, la presencia de metástasis en los ganglios linfáticos, el estado de ER.PR−, expresión negativa de HER2.Conclusiones:Sobre la base de nuestros hallazgos, postulamos que S100A8, S100A9 y TLR5 juegan un papel importante en la progresión del BC y pueden utilizarse como nuevas dianas moleculares para la detección temprana del BC y la predicción para futuras terapias en el BC. (AU)

Evaluation of BRCA1 Large Genomic Rearrangements in Group of Egyptian Female Breast Cancer Patients Using MLPA.

INTRODUCTION: Breast cancer is one of the most widespread cancers affecting women all over the world. In Egypt, it is considered to be the first cause of malignancies among female. BRCA1 Large Genomic Rearrangements (LGRs) have been reported in hereditary breast families and occurs in considerable proportion of cases in various populations. OBJECTIVE AND METHODS: We investigated the incidence of BRCA1 LGRs in group of Egyptian females with breast cancer using Multiplex Ligation-dependent Probe Amplification (MLPA) assay. RESULTS: Thirty six female breast cancer patients were included in this study. There were no BRCA1 LGRs detected in the studied group of patients which does not coincide with other study that were done on a group of Egyptian female patients. DISCUSSION AND CONCLUSION: This variance may be due to the small number of the investigated patients in both studies, which is considered as a limitation. So, screening for LGRs of BRCA1 gene as well as other genes that may be involved in breast cancer such as BRCA2 and CHEK2 genes of a larger number of patients is recommended to get the actual prevalence of these gene in the Egyptian population to deliver a cost-effective primary approach for these patients.

Prognostic significance of the genetic and the immunohistochemical expression of epithelial-mesenchymal-related markers in colon cancer.

BACKGROUND: Epithelial-mesenchymal transition (EMT) is one of the main events in colorectal cancer (CRC) spread. Snail-1 is a zinc transcription factor that mediates EMT in tumor cells probably by down-regulation of E-cadherin and claudin-1. OBJECTIVES: To detect the expression of epithelial markers (claudin-1 and E-cadherin) and mesenchymal markers (snail-1 and vimentin) in primary cancer colon. Also, to select stage II cancer patients of a high risk that can benefit from postoperative adjuvant chemotherapy. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemical analysis were performed to investigate snail-1, claudin-1, E-cadherin and vimentin expressions at mRNA and protein levels in fresh tissues of cancer colon and normal colonic mucosa. The correlations between the expression of these markers and clinicopathological parameters were performed. RESULTS: Normal colonic mucosa revealed complete membranous expression of claudin-1, preserved E-cadherin and negative snail-1 and vimentin expressions. Compared to control, the expression of snail-1 and vimentin mRNA in cancer colon was significantly up-regulated while the expression of claudin-1 and E-cadherin mRNA was significantly down-regulated. These changes were significantly associated with stage and lymph node involvement at both mRNA and protein levels (p< 0.05). There were significant negative correlations between vimentin and each of E-cadherin and claudin-1 gene expression and between snail-1 and each of E-cadherin and claudin-1 gene expression. Moreover, these changes were independent predictors of recurrence of stage II cancer colon cases. CONCLUSION: There is a clinical significance of snail-1, claudin-1, E-cadherin and vimentin as possible markers for recognizing patients with lymph node involvement, advanced stage and high incidence of tumor recurrence in cancer colon.

Prognostic impact of immunohistochemical expression of claudin-4 and epithelial mesenchymal-related markers (Snail-1) in breast invasive duct carcinoma / Impacto pronóstico de la expresión inmunohistoquímica de Claudin-4 y marcadores epiteliales-mesenquimales relacionados (Snail-1) en el carcinoma ductal infiltrante de la mama

Introduction: Although the molecular profile of the breast provides prognostic indicators, risk stratification in breast cancer continues to be a challenge. Therefore, it is mandatory to seek new prognostic markers that could aid the early diagnosis of potential metastases in biopsy samples from breast cancer; among these are increased Snail-1 and Claudin-4 expression.Objectives: The aim of this study was to analyze the correlation between Snail-1 and Claudin-4 with other clinical-pathological parameters and distinct molecular subtypes.Methods: This study included 110 patients with invasive ductal carcinoma from 2009 to January 2015. Snail-1 and Claudin-4 were assessed by immunohistochemistry in formalin-fixed paraffin-embedded tissue blocks and the data were correlated with clinical-pathological data and survival.Results: A total of 65 patients (68.2%) were positive for Snail-1 and 85 patients (77.3%) were positive for Claudin-4. High Snail-1 and high Claudin-4 were detected in high-grade tumors and were associated with lymphovascular infiltration and lymph node metastases (p<0.001 for each). There was a highly significant correlation between Snail-1, Claudin-4 expression and the molecular subtype of breast cancer (p<0.001), with higher Snail-1 expression in TNBC and Her 2/neu cases (p=0.001). Claudina-4 expression in the Her2/neu enriched subtype, Snail-1-positivity and high Claudin-4 expression were associated with recurrence (p=0.001; 0.004 respectively) among the cases studied. Snail-1 and Claudin-4 were inversely related with overall survival (p=0.001) and disease-free survival (p=0.001).Conclusion: High Snail-1 and Claudin-4 levels were associated with adverse outcomes in patients with breast cancer. (AU)

Introducción: Aunque el perfil molecular de la mama proporciona indicadores de pronóstico, la estratificación del riesgo de cáncer de mama sigue siendo un desafío y es obligatoria para buscar nuevos marcadores de pronóstico que puedan facilitar el diagnóstico temprano de metástasis potenciales en las muestras de biopsia de cáncer de mama; entre estos se encuentra la expresión creciente de Snail-1 y Claudin-4.Objetivos: El objetivo de este trabajo es estudiar la correlación de Snail-1 y Claudin-4 con otros parámetros clínico-patológicos y diferentes subtipos moleculares.Métodos: Se inscribieron 110 pacientes con carcinoma de conducto invasivo en este estudio durante el período de enero de 2009 a enero de 2015. Snail-1 y Claudin-4 fueron evaluados por inmunohistoquímica (IHC) en bloques de parafina y los datos se correlacionaron con características clínico-patológicas y de supervivencia.Resultados: Fueron positivos 75 casos (68,2%) para Snail-1 y 85 (77,3%) positivos para Claudin-4. High Snail-1 y High Claudin-4 se detectaron en tumores de alto grado y se asociaron con invasión linfovascular y metástasis en los ganglios linfáticos (p < 0,001 para cada uno). Se detectó una correlación altamente significativa entre Snail-1, la expresión de Claudin-4 y el subtipo molecular de cáncer de mama (p < 0,001), con la mayor expresión de Snail-1 en los casos de cáncer de mama triple negativo (TNBC) y Her 2/neu (p = 0,001). La expresión de Claudina-4 en subtipo Her2/neu enriched, Snail-1 positivo y alta expresión de Claudin-4 se asoció con recaída (p = 0,001; 0,004, respectivamente) entre los casos estudiados. La expresión de Snail-1 y Claudin-4 se relacionó inversamente con la SG (p = 0,001) y la SSE (p = 0,001).Conclusión: Los niveles altos de proteínas Snail-1 y Claudin-4 se asocian con resultados adversos en pacientes con cáncer de mama. (AU)

PARP1, BRCA1 and androgen receptor expression in triple-negative breast cancer patients treated with neoadjuvant chemotherapy / Expresión de receptores de PARP1, BRCA1 y andrógenos en pacientes de cáncer de mama triple negativo tratados con quimioterapia neoadyuvante

Introduction: Triple-negative breast cancer (TNBC) is an aggressive subtype, where no effective therapies have been established for it. Searching for therapeutic targets for TNBC patients is the aim of the current research. Poly adenosine diphosphate ribose polymerase (PARP1) inhibitors are promising antitumor therapy that have a high potency in BRCA1-deficient breast cancers. Materials and methods: Forty TNBC patients who received neoadjuvant chemotherapy (NAC) were enrolled in this study, and evaluated for PARP1, BRCA1, and Androgen receptor (AR) immunohistochemical expression before and after receiving NAC. Data of patients' clinical and pathological responses to the chemotherapy were collected and finally analyzed. Results: The immunohistochemical results revealed 10 cases (25%) positive for AR, while 18 cases (45%) and 22 cases (55%) expressed PARP1 at low and high levels, respectively. Twelve cases (30%) and 28 cases (70%) expressed BRCA1 at low and high levels, respectively. There was a significant difference between PARP1 expression in normal and malignant tissues (P < 0.001). Higher PARP1 expression was correlated with a better overall clinical response (OAR) and pathological complete response (pCR) (P = 0.018, 0.01 respectively). Co-expression of both PARP1 & BRCA1 was correlated with OAR and pCR. Chemotherapy decreases PARP1 protein levels in matched patient samples (P = 0.015). Positive AR expression was correlated with BRCA1 overexpression. Conclusion: PARP1 is highly expressed in TNBC with a better OAR and pCR especially in cases with high BRCA1, so it might be considered as a therapeutic target for this risky group. (AU)

Introducción: El cáncer de mama triple negativo (TNBC) es un subtipo agresivo, donde no se han establecido terapias efectivas para este cáncer. La búsqueda de dianas terapéuticas para pacientes con TNBC es el objetivo de la investigación actual. Los inhibidores de la poli adenosina difosfato ribosa polimerasa (PARP1) son prometedores terapia antitumoral que tienen una alta potencia en los cánceres de mama deficientes de BRCA1. Materiales y métodos: Cuarenta pacientes de TNBC que recibieron quimioterapia neoadyuvante (NAC) se inscribieron en este estudio y se evaluaron para la expresión inmunohistoquímica de PARP1, BRCA1 y receptores de andrógenos (AR) antes y después de recibir NAC. Se recogieron y finalmente se analizaron los datos de las respuestas clínicas y patológicas de los pacientes a la quimioterapia. Resultados: Los resultados inmunohistoquímicos revelaron 10 casos (25%) positivos para AR, mientras que 18 casos (45%) y 22 casos (55%) expresaron PARP1 en niveles bajos y altos, respectivamente. Doce casos (30%) y 28 casos (70%) expresaron BRCA1 en niveles bajos y altos, respectivamente. Hubo una diferencia significativa entre la expresión de PARP1 en tejidos normales y malignos (P 0.001). Una mayor expresión de PARP1 se correlacionó con una mejor respuesta clínica global (OAR) y una respuesta patológica completa (pCR) (P = 0,018, 0,01 respectivamente). La co-expresión de ambos PARP1 y BRCA1 se correlacionó con OAR y pCR. La quimioterapia disminuye los niveles de proteína PARP1 en muestras de pacientes emparejadas (P = 0,015). La expresión positivos de AR se correlacionó con la expresión de BRCA1. Conclusión: El PARP1 está muy expresado en TNBC con una mejor OAR y pCR especialmente en casos con BRCA1 alto, por lo que podría ser considerado como una diana terapéutica para este grupo de riesgo. (AU)

Predictive value of tumor-infiltrating lymphocytes (TILs) and programmed cell death-ligand 1 (PD-L1) expression in breast cancer patients treated with neoadjuvant chemotherapy / Valor predictivo de los linfocitos infiltrantes de tumor, y de la expresión del ligando del factor de muerte celular programada 1 en las pacientes de cáncer de mama tratadas con quimioterapia neoadyuvante

Introduction Immune system plays an important role in behavior of cancer. Breast cancer and its stroma display high levels of immune-cell infiltrates (tumor-infiltrating lymphocytes TILs). Programmed cell death-ligand 1 (PD-L1) is one key inhibitor mechanism for TILs. Potential of TILs and PD-L1 as predictive factors for chemotherapy response in breast cancer is a promising field of study. The aim of this work is to investigate the correlation of PD-L1, TILs and pathologic response following neoadjuvant chemotherapy (NAC) in breast cancer patients and effect of NAC on PD-L1 expression and TILs in residual tumor mass.MethodsThirty patients with invasive duct carcinoma diagnosed by core biopsy and received NAC were enrolled in this prospective study from November 2018 to October 2020. PD-L1 expression was evaluated by immunohistochemistry and relates this to TILs, clinical characteristics, and response to neoadjuvant chemotherapy and then re-evaluated in residual masses after surgery.ResultsPD-L1 expression was observed in 40% of cases in the tumor cells. High stromal TILs were detected in 46.7%. Also, 64.3% and 58.3% of patients expressed TILs and PD-L1 (respectively) in their core biopsies gained complete clinical and pathologic responses with significant difference (p value<0.001; 0.013). High PD-L1 expression and high TILs were observed in triple negative breast cancer (TNBC) and Her2 enriched cases but without significant difference.ConclusionHigh TILs and PD-L1 are associated with complete clinical and pathologic responses in breast cancer patients who receiving NAC.(AU)

Introducción El sistema inmune juega un papel importante en el comportamiento del cáncer. El cáncer de mama y su estroma exhiben altos niveles de infiltrados de las células inmunitarias (linfocitos infiltrantes de tumor [TIL]). El ligando del factor de muerte programada 1 (PD-L1) es un mecanismo inhibidor clave para los TIL. El potencial de TIL y PDL-1 como factores predictivos para la respuesta a la quimioterapia en el cáncer de mama es un campo de estudio prometedor. El objetivo de este estudio es estudiar la correlación de PD-L1, TIL y la respuesta patológica tras la quimioterapia coadyuvante (NAC) en pacientes con cáncer de mama, así como el efecto de NAC en la expresión de PDL-1 y TIL en la masa tumoral residual.MétodosSe incluyó en este estudio prospectivo a 30 pacientes con carcinoma ductal invasivo diagnosticadas mediante biopsia central, que recibieron NAC de noviembre de 2018 a octubre de 2020. La expresión de PD-L1 fue evaluada mediante inmunohistoquímica, y fue relacionada con TIL, características clínicas y respuesta a la quimioterapia neoadyuvante, reevaluándose en masas residuales tras la cirugía.ResultadosLa expresión de PD-L1 se observó en el 40% de los casos en las células tumorales. Se detectaron altos niveles de TIL estromales en el 46,7% de los casos. De igual modo, el 64,3 y el 58,3% de las pacientes con expresión de TIL y PDL-1, respectivamente, en sus biopsias centrales logró respuestas clínicas y patológicas completas con diferencia significativa (p<0,001; 0,013). La alta expresión de PDL1 y los altos niveles de TIL fueron observados en el cáncer de mama triple negativo (TNBC) y en los casos de Her2 enriquecido, aunque sin diferencia significativa.ConclusiónLa alta expresión de TIL y PDL1 se asocia a respuestas clínicas y patológicas completas en las pacientes de cáncer de mama que reciben NAC.(AU)