ECP 2023 Abstracts
S297 Virchows Archiv (2023) 483 (Suppl 1):S1–S391 13 Background & objectives: Agnostic biomarkers are predictive and independent from histological type and site. In this study, the status of agnostic and potential agnostic markers in laryngeal squamous cell carcinomas were analysed by in silico analysis method. Methods: In this study, cBioPortal for Cancer Genomics database pro- viding open access bioinformatics service was used. The genes most frequently mutated and showing copy number changes were examined. Additionally, the mutation status of agnostic markers (microsatellite markers, tumour mutation load, NTRK, BRAF, RET) and potential agnostic markers (KRAS, HER2, PIK3CA, NRG1, FGFR, MET) and also the relationship with prognosis was determined. Results: The first three genes that mutated most frequently were TP53 (87.4%), LRP1B (29.7%), NSD1 (28.8%), while the first three genes with copy number changes were P3H2 (36.2%), CDKN2A (35.3%), TP63. (35.3%). Mutation rates of agnostic markers were MLH1 (0.9%), MSH2 (0.9%), MSH6 (1.8%), PMS2 (0.9%), NTRK3 (4.5%), BRAF (2.7%), and RET (5.4%). The rate of tumours with a tumour mutation- load ≥10 was 34.3%, and there were more mutations in twelve genes in this group (p<0.001). Methylation was detected in more genes in cases with tumour mutation load <10 (p<0.05). Mutation rates in potential agnostic markers were PIK3CA (19.8%), ALK (2.7%), MET (1.8%), EGFR (0.9%), FGFR2 (0.9%) and FGFR4 (% 0.9). Conclusion: Tumour mutation burden and PIK3CA may be important agnostic markers in laryngeal squamous cell carcinomas, while the other agnostic and potential agnostic biomarker positivity is rare. E-PS-12-060 Determining clinically relevant histopathological parameters of the invasive margin in head and neck squamous cell carcinomas S. Tzorakoleftheraki*, T. Koletsa, K. Markou, S. Chrisafi, E. Daskalaki, E. Sgouramali, P. Hytiroglou, V. Kotoula *Department of Pathology, School of Medicine, Aristotle University of Thessaloniki, Greece Background & objectives: To investigate the patterns and prognostic impact of histological parameters along the invasive margin (IM) in head and neck squamous cell carcinomas (HNSCCs). Methods: We examined the IMof 83 HNSCCs (73.5% laryngohypopharyn- geal; 21.7% oral cavity; 4.8% oropharyngeal). We recorded the following histologic parameters: percentage of keratinization and mature cells; cellular atypia and pleomorphism; worst pattern of invasion (WPOI); lymphocytic host response (LHR) and presence of perineural invasion (PNI). We evalu- ated the association of these parameters with patient overall survival (OS). Results: Most HNSCCs (67/83; 80.7%) were devoid of keratiniza- tion in the IM. Twenty-seven (32.5%) HNSCCs revealed >51% mature cells. The vast majority presented moderate to severe pleomorphism and atypia (65/83; 78.3% and 75/83; 90.4%, respectively). WPOI showed heterogeneity in a considerable number of tumours (33/83; 39.8%). Large neoplastic islands were predominant (35/83; 42.2%), followed by small groups and finger-like infiltration. Pushing borders and satellites were infrequent. Different patterns of LHR were equally distributed among HNSCCs. Nine (10.8%) HNSCCs presented PNI, 2 of which invaded nerves >1mm. Dense LHR was beneficial for patient outcome (p<0.0001), while PNI adversely affected OS (p=0.0160). Conclusion: The evaluation of the IM in HNSCCs is important for deter- mining patient prognosis. Even though WPOI was not associated with patient outcome, LHR density and PNI proved to be significant prognos- ticators. These parameters are easily and cost-effectively examined on H&E. Their assessment may be incorporated in daily practice, in order to provide further clinically relevant information in histology reports. E-PS-12-061 Report of rare malignant tumour of the larynx: spindle cell squa- mous cell carcinoma (SCSCC) with heterologous component of malignant chondroid differentiation E. Vouza*, M. Theodorakopoulou, E. Boltetzou *General Hospital of Athens “ELPIS”, Greece Background & objectives: SCSCC represents less than 1% of laryn- geal cancers. It’s consisting of spindle cells that are epithelial in nature, and/or component of squamous epithelium with dysplasia, carcinoma in situ with or without infiltration. In 7% of cases, heterologous ele- ments are observed. Methods: We report a case of a 66-year-old-man, with long smoking history, that presented dysphonia and dyspnea the last two months. During a laryngoscopy an exophytic polypoid tumour of the glottis was revealed and biopsies were taken and sent to pathology department. We received a biopsy-material of whitish/grey colour, which entirely submitted to microscopic examination. Results: The microscopy revealed tumour segments consist from hyperchromatic spindle cells and high pleomorphic cells within a myxoid or chondromyxoid stroma. There were also seen areas of heterologous malignant chondroid differentiation. Though most of the biopsies were ulcerated, adjacent to invasive compo- nent, a focally preserved surface squamous epithelium, was also found. The epithelium showed features of carcinoma in situ. Immunohistochemically, the spindle-cell component of the tumour was strongly positive for vimentin, weakly positive for cytokeratin AE1/AE3 and S100, focal positive for p63, CK5/6, SMA and nega- tive for EMA, Melan-A, CK7 and CK20. All the above findings supported diagnosis of spindle squamous cell carcinoma. Conclusion: Spindle cell squamous carcinoma is a rare malignancy that poses diagnostic and therapeutic challenges. The spindle cell component usually represents the largest part of the tumour and constitutes a diagnostic challenge given morpho- logic overlap with fibrosarcoma, leiomyosarcoma, malignant mela- noma and inflammatory myofibroblastic tumour. The presence of epithelial component in the biopsy samples is essential for correct diagnosis. SCSCC is more aggressive than squamous carcinoma, with highly recurrence and tendency towards lymphatic metastasis. A wide local excision is recommended. E-PS-12-062 Expression of MMPs in assessing the effectiveness of therapy in patients with chronic generalised periodontitis V. Zakharava*, L. Kazeko, J. Benesh *N.N.Alexandrov National Cancer Centre of Belarus, Belarus Background & objectives: The study of the expression of matrix metalloproteinases is important for understanding the pathogenesis of periodontitis and for the opportune treatment selection. Objective was to study the levels of metalloproteinases expression before the therapy and at intervals of 1,3,6,9,12 months. Methods: Gingival biopsy from patients with chronic periodontitis (n=18) was immunostained (IHC) with metalloproteinases -1,-2,- 8,-9,-14. Image analysis of cytoplasmic expression was performed using AperioImageScopev12.4.0. Therapy included gingival curet- tage with insertion of an antiseptic pledget containing hemostatic sponge with tricalcium phosphate, eugenol and iodoform in peri- odontal pockets; NSAIDs were used in case of suppuration. Results: A wave-like dynamics of the MMPs levels during the course of periodontitis treatment was revealed. At initially low levels of MMPs at the disease manifestation: a tendency to an increase of MMP1 expression levels by 6 and 12 months of observation was found. At initially high levels of MMPs expression: a progressive decrease in MMP2 and MMP9 expression by 6 and 12 months of follow-up, a decrease in MMP8 expression by 3 month with minimal levels during follow-up, a decrease of MMP14 expression by 6 month with a subsequent increase by 12 month was found.
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