Correlation of PD-L1 immunohistochemical expression with microsatellite instability and p53 status in endometrial carcinoma.

Background: Endometrial carcinoma (EC) is the most common gynaecological cancer worldwide. The Cancer Genome Atlas molecular grouping of a given case of EC could be assessed by POLE gene mutation, mismatch repair (MMR) 'to reflect microsatellite instability' and p53 status, which has proved to be of prognostic value. Programmed cell death receptor 1 (PD-1) and its ligand (PD-L1) are playing a progressively important role in tumour immunology and cancer treatment. Objectives: To investigate PD-L1 immunohistochemical expression in EC in relation to MMR and p53 status. Associations between marker expression and different histopathological parameters were also investigated. Methods: This retrospective study was performed on archival biopsies of 170 cases of EC using a tissue microarray model. Immunohistochemical staining was applied using antibodies against PD-L1, MLH1, MSH2 and p53. Results: The percentages of positivity were as follows: PD-L1, 19.6%; MLH1, 79.5%; MSH2, 78.5%; and p53 mutant, 13.8%. There was significant correlation between MLH1 expression and MSH2 expression (p = 0.008). Tumour grade was significantly correlated with stage (p = 0.005) and p53 mutant expression (p = 0.008). Combined PD-L1 positivity and MMR deficiency showed significant correlation with the presence of lymphovascular space invasion (p = 0.014). MSH2 negativity was significantly associated with poorer overall survival (p = 0.014). Conclusions: A panel of immunohistochemical markers (PD-L1, MLH1, MSH2 and p53) could help to predict the prognosis and plan the treatment of patients with EC. MMR deficiency seems to be a good predictor for PD-L1 status, and therefore the response to potential PD-1/PD-L1 inhibitor therapy.

Potential Role for a Panel of Immunohistochemical Markers in the Management of Endometrial Carcinoma.

BACKGROUND: In order to improve the efficacy of endometrial carcinoma (EC) treatment, identifying prognostic factors for high risk patients is a high research priority. This study aimed to assess the relationships among the expression of estrogen receptors (ER), progesterone receptors (PR), human epidermal growth factor receptor 2 (HER2), Ki-67, and the different histopathological prognostic parameters in EC and to assess the value of these in the management of EC. METHODS: We examined 109 cases of EC. Immunohistochemistry for ER, PR, HER2, and Ki-67 were evaluated in relation to age, tumor size, International Federation of Gynecology and Obstetrics (FIGO) stage and grade, depth of infiltration, cervical and ovarian involvement, lymphovascular space invasion (LVSI), and lymph node (LN) metastasis. RESULTS: The mean age of patients in this study was 59.8 ± 8.2 years. Low ER and PR expression scores and high Ki-67 expression showed highly significant associations with non-endometrioid histology (p = .007, p < .001, and p < .001, respectively) and poor differentiation (p = .007, p < .001, and p <. 001, respectively). Low PR score showed a significant association with advanced stage (p = .009). Low ER score was highly associated with LVSI (p = .006), and low PR scores were associated significantly with LN metastasis (p = .026). HER2 expression was significantly related to advanced stages (p = .04), increased depth of infiltration (p = .02), LVSI (p = .017), ovarian involvement (p = .038), and LN metastasis (p = .038). There was a close relationship between HER2 expression and uterine cervical involvement (p = .009). Higher Ki-67 values were associated with LN involvement (p = .012). CONCLUSIONS: The over-expression of HER2 and Ki-67 and low expression of ER and PR indicate a more malignant EC behavior. An immunohistochemical panel for the identification of high risk tumors can contribute significantly to prognostic assessments.

Ectonucleoside triphosphate diphosphohydrolase-1 (E-NTPDase1/CD39) as a new prognostic marker in chronic lymphocytic leukemia.

Numerous prognostic markers were introduced to screen for patients with B-cell chronic lymphocytic leukemia (B-CLL) likely to have a progressive course, bearing the potential to facilitate risk-adapted treatment strategies. Extracellular adenosine triphosphate (ATP) functions as a "natural adjuvant" that boosts immune response in the tumor microenvironment. Ectonucleoside triphosphate diphosphohydrolase-1 (CD39/ENTPD1) is the ectonucleotidase that catalyzes the hydrolysis of ATP. The present study was conducted to analyze CD39 expression in T cells and B-CLL cells to evaluate its impact on the clinical course of patients with B-CLL and correlate its levels with well-established risk factors. T-cell CD39 expression was significantly increased in patients' peripheral blood compared to healthy controls. The higher levels were associated with advanced stages of disease and negatively interacted with time to first treatment. Overall, our data indicate that T-cell CD39 expression may identify subsets of patients with B-CLL with an unfavorable clinical outcome. Moreover, it can be incorporated into prognostic schema to improve the prediction of CLL disease progression.

Pentoxifylline and local honey for radiation-induced burn following breast conservative surgery.

INTRODUCTION: Breast-conserving therapy is currently the standard of management of breast cancer cases. Radiotherapy is an integral part of it; however, it has several complications. Radiation induced burn is a common complication of radiotherapy that requires more effective lines of management rather than the classically used ones. We investigated whether the addition of pentoxifylline (PTX) alone or in combination with topical honey is effective in its management compared to the standard measures. METHODS AND MATERIALS: In this prospective study, patients were randomly allocated into three groups each of 50 cases. Group A received standard burn treatment (control group). Group B received additionally 400 mg PTX twice daily. Group C received the same treatment as Group B with adding topical purified honey ointment. Patients were assessed initially and subsequently after 4 and 12 weeks, for projected coetaneous surface area (PCSA) of burn, pain severity, limitation of movement and exudation. RESULTS: There was a striking regression of the mean PCSAs of lesions among groups B and C at 12 weeks, with reduction rates (86±61%) and (76±58%) respectively (p<0.0001***). The addition of honey was associated with marked pain relieving effect and rescue of proper motion. Finally, honey was associated with shorter duration of treatment as 74% of group C patients completely recovered after 12 weeks, compared to only 54% and 36% of groups B and A in order. CONCLUSION: Combination of PTX and honey is an ideal measure for treatment of radiation-induced burn following breast conservative surgery.