Browsing by Author "Zablocka, Tatjana"

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    Addressing the importance of melanoma tumor-infiltrating lymphocytes in disease progression and clinicopathological characteristics
    (2021-12) Zablocka, Tatjana; Nikolajeva, Anna; Kreismane, Madara; Pjanova, Dace; Isajevs, Sergejs
    Tumor-infiltrating lymphocytes (TILs) in primary cutaneous melanoma are considered to represent the host's antitumor immunological response; however, whether there are associations between TIL grade and histopathological characteristics and disease survival remains controversial. BRAF mutational status has been established as a routine screening method in advanced malignant melanoma, and worse prognosis rates have been demonstrated in patients harboring BRAF mutations. However, the general impact of BRAF mutational status on survival and histopathological characteristics is still debated. The aim of the present study was to compare the value of the assessment of TIL grade in stages I-II nodular and superficial spreading melanoma and BRAF mutational status, and its influence on clinicopathological characteristics. Altogether, 85 patients at stage IA-IIC who underwent melanoma surgical treatment at the Riga East University Hospital between 2012 and 2017 were retrospectively enrolled in the study. The histopathological characteristics were assessed according to the current World Health Organization and The American Joint Committee on Cancer 8th edition guidelines. The current study showed that patients with melanoma with high TIL grade had significantly better progression-free survival than patients with low TIL grade (hazard ratio, 4.9; 95% CI, 2.3-11.2; P<0.0001). BRAF mutations were observed in 52 patients (61.2%). BRAF mutational status in melanoma was associated with Clark invasion level (P=0.045), patient age (P=0.02) and TIL (P=0.04). The assessment of TIL grade in stage I-II melanoma demonstrated prognostic significance value and may help improve risk assessment in the future.
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    Effects of BRAF V600E and NRAS mutational status on the progression-free survival and clinicopathological characteristics of patients with melanoma
    (2023-01) Zablocka, Tatjana; Kreismane, Madara; Pjanova, Dace; Isajevs, Sergejs
    Hotspot mutations of the BRAF and NRAS genes are the most common genetic alterations in invasive cutaneous melanoma; however, the prognostic significance of BRAF and NRAS co-mutations remains controversial. The present study aimed to determine the association between NRAS and BRAF mutation status and the clinicopathological characteristics of patients with stage IA-IIC melanoma. A total of 118 patients who underwent surgical treatment for stage IA-IIC melanoma at the Riga East University Hospital between 2012 and 2018 were retrospectively enrolled in the present study. BRAF and NRAS mutation status was assessed by digital droplet PCR using the BRAFV600, NRAS Q61 and NRAS G12/G13 Screening Assays. The association between mutation status and clinicopathological features and progression-free survival (PFS) was then analyzed. The BRAF V600 mutation was detected in 67 out of 118 patients (56.8%). The PFS did not differ between patients with BRAF wild-type and BRAF-mutant melanoma. NRAS mutations were detected in 35 out of 118 patients (29.6%). The NRAS mutational status was associated with Breslow thickness (P=0.035), tumor type (P=0.020; χ2=0.20), mitotic rate (P=0.025) and lymphovascular invasion (P=0.02; χ2=0.20). Patients with NRAS-mutant melanoma had significantly worse PFS compared with NRAS wild-type melanoma (HR=12.30; 95% CI=5.78-26.21, P<0.0001). Furthermore, BRAF and NRAS co-mutant melanoma was associated with a significantly worse PFS compared with BRAF-mutant melanoma (HR=6.30; 95% CI=3.10-12.70, P<0.0001). In conclusion, NRAS-mutant and NRAS/BRAF co-mutant stage IA-IIC melanoma was associated with worse PFS compared with NRAS wild-type and BRAF-mutant melanoma. The assessment of NRAS mutation status in melanoma in routine clinical practice may be beneficial for the risk stratification of disease progression for primary non-metastatic malignant melanoma.
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    Management of a primary malignant melanoma of uterine cervix stage IVA patient with radical surgery and adjuvant oncolytic virus Rigvir(R) therapy: A case report.
    (2020-05-22) Pumpure, Elizabete; Dručka, Eva; Kigitoviča, Dana; Meškauskas, Raimundas; Isajevs, Sergejs; Nemiro, Ineta; Rasa, Agnija; Olmane, Evija; Zablocka, Tatjana; Alberts, Pēteris; Doniņa, Simona
    Primary malignant melanoma of the uterine cervix is a rare disease with poor prognosis and high recurrence rate. We used Rigvir® as adjuvant therapy for a stage IVA patient. Tolerability, overall and progression-free survival are good.
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    Stage IIA Skin Melanoma Treatment With ECHO-7 Oncolytic Virus Rigvir
    (2022-09-14) Čēma, Ingrīda; Kleina, Regīna; Doniņa, Simona; Isajevs, Sergejs; Zablocka, Tatjana; Rasa, Agnija; Alberts, Pēteris; Rīga Stradiņš University; Faculty of Medicine; Institute of Microbiology and Virology
    Melanoma is a global problem due to the rising numbers of skin melanoma cases. Current treatment guidelines for patients with stage IIA melanoma recommend only observation after surgery. In this report, the authors describe a patient with stage IIA skin melanoma treated with surgery and Rigvir virotherapy. Two years after the patient discovered a brown spot on the right cheek, surgery was indicated because the mass had started to ulcerate. Rigvir virotherapy was applied both before and after surgery. Observations made more than 7 years after surgery indicated no signs of disease progression. This case report illustrates an early treatment approach. Neoadjuvant treatment for early-stage melanoma is gaining more interest in both scientific and medical communities; therefore, the authors believe it is relevant to share their observations.
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    Upregulation of FOXP3+Regulatory T Lymphocytes and CD8+Lymphocytes in Patients with High-Grade Squamous Intraepithelial Lesions Correlated with HPV Infection
    (2022-04) Mitiļdžans, Androniks; Zablocka, Tatjana; Isajevs, Sergejs; Gordjušina, Valentina; Rezeberga, Dace; Department of Obstetrics and Gynaecology
    Modern therapeutic strategies for precancerous cervical intraepithelial neoplasia (CIN) focus on immune-modulatory and cancer vaccination. The local cervical immune status in cervical cancer and CIN could influence HPV infection persistence, progression and carcinogenesis. We analysed the role of FOXP3+ regulatory T lymphocytes, CD4+ and CD8+ T lymphocytes in CIN I, CIN II and CIN III patients with and without HPV infection. Sixty-two patients were enrolled in the study. Each patient underwent a colposcopy-guided cervical biopsy. FOXP3+ lymphocytes and CD4+,CD8+ lymphocytes were detected by immunostaining in tissue samples obtained from a control group (n = 10), patients with CIN I (n = 20), CIN II (n = 14) and CIN III (n = 18) lesions. HPV was assayed by Aptima. The results showed that the numbers of CD4+ T lymphocytes did not differ between patients with CIN I, CIN II, and CIN III. However, patients with CIN II and CIN III had significantly upregulated CD8+T lymphocytes compared to patients with CIN I. In addition, patients with CIN II and CIN III had increased FOXP3 + T lymphocytes compared with patients with CIN I, which was associated with HPV status. Upregulation of FOXP3+ regulatory T lymphocytes and CD8-positive lymphocytes in patients with CIN II and CIN III suggested a pivotal role of T regulatory lymphocytes and CD8+ lymphocytes for counteracting the host immune response in the progression from CIN I to CIN II and CIN III.