Effectiveness and Safety of Immune Checkpoint Inhibitors in Older Cancer Patients.

BACKGROUND: The development of immunotherapy checkpoint inhibitors (ICIs) has revolutionized cancer care. However, old patients are underrepresented in most clinical trials, although they represent a significant proportion of real-world patients. We aimed to evaluate the effectiveness and safety of ICIs in patients older than the age of 70. METHODS: We performed a retrospective chart review of 145 patients aged 70 or older treated with ICIs for metastatic or unresectable cancer. RESULTS: Median progression-free survival (PFS) was 10.4 months (95% CI 8.6-13.7), with no differences between octogenarians and septuagenarians (p = 0.41). Female gender (p = 0.04) and first-line treatment setting (p < 0.0001) were associated with a longer median PFS. Median overall survival (OS) was 20.7 months (95% CI 13.5-35.0 months), with no difference based on performance status, cancer site, gender, or between septuagenarians and octogenarians (all p > 0.005). Patients treated with ICIs in the first-line setting reported longer OS compared to treatment in the second-line setting (p < 0.001). Discontinuation of ICIs due to adverse effects was associated with both shorter PFS (p = 0.0005) and OS (p < 0.0001). CONCLUSION: The effectiveness of ICIs in older cancer patients primarily depends on the line of treatment and treatment discontinuation. Octogenarians experienced similar treatment responses, PFS, OS, and adverse effects compared to septuagenarians.

Prostate Cancer Scoring Index for Risk of Progression of Radioresistant Disease.

Prostate cancer (Pca) is among the most common malignant diseases in men and the fourth leading cause of death worldwide. Surgery and radical radiotherapy (RT) remain the gold standard for the treatment of localized or locally advanced prostate cancer. The efficiency of radiotherapy treatment is limited by toxic side effects due to dose escalation. Cancer cells often develop radio-resistant mechanisms that are related to the DNA repair, inhibition of apoptosis or changes in cell cycle. Based on our earlier research on biomarkers that are involved in those cellular mechanisms (p53, bcl-2, NF-kb, Cripto-1 and Ki67 proliferation) and correlation with clinico-pathological parameters (age, PSA value, Gleason score, grade group, prognostic group), we created the numerical index for risk of tumor progression in patients with radioresistant tumors. For each of these parameters, the strength of association with disease progression was statistically assessed, and a specific number of points was assigned proportional to the strength of the correlation. Statistical analysis identified an optimal cut-off score of 22 or more as an indicator of significant risk for progression with a sensitivity of 91.7% and a specificity of 66.7%. The scoring system in the retrospective receiver operating characteristic analysis showed AUC of 0.82. The potential value of this scoring is the possibility of identifying patients with clinically significant radioresistant Pca.

PD-L1 expression is regulated by microphthalmia-associated transcription factor (MITF) in nodular melanoma.

Malignant melanoma (MM) is known to avoid the host's immune response. Studies on in vitro melanoma cell lines link the microphthalmia-associated transcription factor (MITF) with the regulation of the PD-L1 expression. It seems that MITF affects the activation of the gene responsible for PD-L1 protein expression. Several proteins, including Bcl-2 and Cyclin D1, play major roles in malignant melanoma cell cycle regulation and survival. Our study aims to assess the relationship between MITF, Bcl-2, and cyclin D1 protein expression and the expression of the PD-L1 molecule. Additionally, we examined the association of BRAF mutation, MITF, and CCND1 gene amplification with PD-L1 protein expression. We performed immunohistochemical staining on fifty-two tumour samples from patients diagnosed with nodular melanoma (NM). BRAF V600 mutation, MITF, and CCND1 gene amplification analyses were analyzed by the Sanger sequencing and QRT-PCR methods, respectively. Statistical analyses confirmed the significant inverse correlation between cyclin D1 and PD-L1 expression (p = 0.001) and correlation between PD-L1 and MITF protein expression (p = 0.023). We found a statistically significant inverse correlation between the present MITF gene amplification and PD-L1 (p = 0.007) and MITF protein expression (p = 3.4 ×10-6), respectively. Our study, performed on clinical NM materials, supports the in vitro study findings providing a rationale for the potential MITF-dependent regulation of PD-L1 expression in malignant melanoma.

Pancreatic Carcinoma Metastatic to the Gingiva.

Metastatic tumors to the oral cavity are uncommon, representing approximately 1% of all cases of oral malignant lesions even when a metastatic disease is present. The 53-year-old female is presented complaining of abdominal pain, weight loss, and a loose stool recurring not more than three times per day. A computed tomography (CT) scan of the abdomen showed a retroperitoneal mass expanding along the body of the pancreas. Colonoscopy and gastroscopy with a gastric mucosa biopsy showed a normal result. After laparoscopic surgery, the primary site of adenocarcinoma was not confirmed. The patient was referred to the Maxillofacial Surgery Clinic with pain, swelling, and occasional bleeding around the lower right second mollar. Immunohistochemicaly, the tumor cells were positive for Cytokeratin (CK) 19, Cytokeratin (CK) 7, and homebox protein (CDX-2), which are highly sensitive markers of pancreatobiliar cancer. Therefore, the patient was diagnosed with pancreatic carcinoma. This report describes a rare metastasis of malignant pancreatic tumor to the lower right gingiva and highlights the importance of immunohistochemical examination and how it helped identify both the origin and the nature of gingival neoplasm.

Matrix metalloproteinases MMP-1, MMP-2, and MMP-13 are overexpressed in primary nodular melanoma.

BACKGROUND: The spread and invasion of malignant melanoma cells involve degradation and reorganization of the extracellular matrix by the activation of several matrix metalloproteinases (MMPs). This study analyzed the expression of MMP-1, MMP-2, and MMP-13 proteins in primary nodular melanoma (NM) and dysplastic nevi (DN) as a significant risk factor for melanoma development. The secondary goal was to analyze the correlation of MMPs protein expression in NM with tumor invasion, BRAF V600 mutation status, and overall survival. METHODS: Immunohistochemistry for MMP-1, MMP-2, and MMP-13 was performed on nodular melanoma (n = 52) and dysplastic nevi (n = 28) on tissue microarray (TMA). BRAF V600 mutation analysis on NM samples was performed by the Sanger sequencing method. RESULTS: A high level of MMPs expression in NM samples (>30%) compared with DN (<8%) was statistically significant (P < 0.001). BRAF V600 mutations were detected in 15 of 39 (38.5%) NM samples. This study revealed an interesting finding that MMP-1 and MMP-13 protein expression in the BRAF V600 mutated melanomas were significantly lower than in the BRAF V600 wild type (P < 0.05). CONCLUSION: Cox analysis revealed that Clark categories, Breslow thickness, and MMP-1 high protein expression are predictive factors for shorter overall survival (P < 0.05).

Recurrent amelanotic melanoma of nasal cavity: Biological variability and unpredictable behavior of mucosal melanoma. A case report.

The aim of this report is to present a case of a patient with a recurrent nasal cavity amelanotic melanoma (AM), with emphasis on diagnosis and therapy options of this clinical entity. A 65-year-old female patient presented with pain in the right cheek region and nasal obstruction. In 2013, she was diagnosed with mucosal melanoma (MM) of the left nasal cavity. After endoscopic surgery and radiotherapy, the patient was followed by the oncology team. Five years after the initial diagnosis, rhinoscopy showed a tumorous formation in the right nasal cavity. The tumor mass was without black discoloration and was the same color as the surrounding nasal mucosa. Microscopic examination after biopsy of the tumor confirmed amelanotic MM. The patient underwent an additional endoscopic surgery. A complete standard diagnostic workup for MM found metastases in head and neck lymph nodes, on both sides. MMs of head and neck are uncommon malignancies. Unique biology of MM cells causes a high rate of recurrences. This report presents an example of recurrent AM of the nasal cavity, in treatment with checkpoint inhibitor (pembrolizumab), which could provide a good therapy option for patients with MM.

Immunohistochemical analysis of vocal cord polyps applying markers of squamous cell carcinogenesis.

OBJECTIVE: The aim of the study was to perform a pathohistological and immunohistochemical analysis of squamous cell (SC) carcinogenesis markers on epithelial linings of vocal cord polyps. The vocal box, being a heavily burdened organ with intensive cell renewal and regenerative processes, is therefore a favourable environment for constant epithelial growth and hyperplasia. In our ongoing projects on laryngeal carcinogenesis and research on laryngeal tissue, we encountered atypia on diagnosed nodules and polyps that are usually considered as benign formations, resulting from the above-mentioned cell renewal and regeneration, which lead to further investigation. The purpose was to see if changes in molecular markers of SC carcinogenesis follow, or, may appear in immunohistochemical (IHC) analysis, before histological atypia in standard haematoxylin-eosin (HE) staining, and contribute in early diagnosis of potentially suspect polyps. METHODS: After classical pathohistological (PH) analysis on HE slides, IHC analysis of EGFR, cyclin D1, p53, Ki-67, and IMP3 was performed on tissue microarrays of laryngeal tissue (50 samples), ranging from normal to hyperplastic lesions with no atypia (34 samples), low-grade atypia (11 samples), and high-grade atypia (5 samples). RESULTS: This study established an increase and correlation of EGFR, cyclin D1, p53, Ki-67 and IMP3 IHC expressions with pathohistological findings of dysplasia in glottic polypoid lesions. Low and high-grade dysplasia had statistically higher percentages of EGFR-positive cells than normal epithelium and simple hyperplasia (SH) (low vs. normal/SH P = 0.007; high vs. normal/SH P = 0.001). High-grade dysplasia had statistically more positive cells than low-grade dysplasia (P = 0.004), and low-grade dysplasia had statistically more positive cells than specimens without atypia (P = 0.007). The percentage of positive cells was statistically higher for cyclin D1, p53 and Ki-67 in high-grade dysplasia versus low-grade dysplasia (cyclin D1 P = 0.011, p53 P = 0.002; Ki-67 P = 0.026; respectively) and versus normal epithelium and SH (cyclin D1 P = 0.003; p53 P = 0.001; Ki-67 P = 0.002; respectively). An increase of IMP3-positive cells with an increase of atypical changes in the laryngeal epithelium, from superficial towards basal layers was noticed, contrary to the usually seen positivity pattern of SC carcinogenesis markers from basal to superficial layers. A statistically significant difference of IMP3 IHC staining between the pathohistological groups (P = 0.003) was recorded. CONCLUSION: Only polyps that present with simple hyperplasia as the greatest mucosal change can be considered as benign formations. Pathohistologically detected atypia in polypoid changes of vocal cords, confirmed by molecular atypia with an increase of SC carcinogenesis markers, suggest their inclusion in studies of laryngeal carcinogenesis. Our results suggest that in problematic cases IHC analysis could be of interest in detection of biological aggressiveness in polypoid laryngeal tissue and beneficiary for polyp patients' follow-up. Further research of laryngeal carcinogenesis markers and their meaning in fibrovascular polyps is of interest.

Kaposi's sarcoma in an HIV-negative chronic lymphocytic leukemia patient without immunosuppressive therapy: A case report.

Kaposi's sarcoma is a neoplasm of endothelial cells. That vascular tumor is usually limited to the skin, but it may involve mucous membranes, visceral organs, and lymph nodes. Serological evidence has shown that human herpesvirus 8 infection is required for the development of Kaposi's sarcoma. Chronic lymphocytic leukemia is the most common leukemia all over the world. Increased skin cancer risk has been reported for patients with chronic lymphocytic leukemia. The relation between these two pathologies has not yet been clarified. We report a case of Kaposi's sarcoma along with chronic lymphocytic leukemia in a patient who did not receive therapy for chronic lymphocytic leukemia.