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Autophagy is a biological process that facilitates the degradation and removal of damaged structures and macromolecules. In neoplasms, autophagy has been proposed to play a dual role, functioning either as a tumor promoter or a tumor suppressor. To date, no comprehensive analysis of autophagy, primarily through immunohistochemical investigation of autophagy-related proteins (ATGs), has been conducted in chordomas (CHs), which are rare bone tumors that arise from remnants of the notochord. The present study aimed to investigate the immunoexpression of several ATGs, including microtubule-associated protein 1 light chain 3 (LC3A/B), Sequestosome-1 (p62) and autophagy and Beclin 1 regulator 1 (AMBRA-1) in a series of sporadic adult conventional clival CHs collected from a single neuropathological center in southern Italy. Immunohistochemical analysis revealed that LC3A/B, p62 and AMBRA-1 were exclusively found in neoplastic cells, with no expression detected in the surrounding stromal cells. Both LC3A/B and p62 were expressed in the cytoplasm and nucleus of neoplastic cells, while AMBRA-1 was predominantly localized in the cytoplasm. In all cases of CHs, p62 was consistently and highly expressed, whereas a similarly high expression of LC3A/B was observed in five cases, four of which were characterized by neoplastic recurrence and partial resection. Low immunoreactivity was noted in seven out of 10 cases (70%), while three recurrent cases exhibited high levels of AMBRA-1 immunostaining. Statistical analysis using Fisher's exact test revealed significant P-values for LC3A/B (P=0.048), AMBRA-1 (P=0.033), Ki-67 (P=0.048) and surgical treatment (P=0.048). Consequently, a negative prognostic role for these two ATGs may be hypothesized in the development of CHs. [ABSTRACT FROM AUTHOR]

Autophagy is a biological process that facilitates the degradation and removal of damaged structures and macromolecules. In neoplasms, autophagy has been proposed to play a dual role, functioning either as a tumor promoter or a tumor suppressor. To date, no comprehensive analysis of autophagy, primarily through immunohistochemical investigation of autophagy-related proteins (ATGs), has been conducted in chordomas (CHs), which are rare bone tumors that arise from remnants of the notochord. The present study aimed to investigate the immunoexpression of several ATGs, including microtubule-associated protein 1 light chain 3 (LC3A/B), Sequestosome-1 (p62) and autophagy and Beclin 1 regulator 1 (AMBRA-1) in a series of sporadic adult conventional clival CHs collected from a single neuropathological center in southern Italy. Immunohistochemical analysis revealed that LC3A/B, p62 and AMBRA-1 were exclusively found in neoplastic cells, with no expression detected in the surrounding stromal cells. Both LC3A/B and p62 were expressed in the cytoplasm and nucleus of neoplastic cells, while AMBRA-1 was predominantly localized in the cytoplasm. In all cases of CHs, p62 was consistently and highly expressed, whereas a similarly high expression of LC3A/B was observed in five cases, four of which were characterized by neoplastic recurrence and partial resection. Low immunoreactivity was noted in seven out of 10 cases (70%), while three recurrent cases exhibited high levels of AMBRA-1 immunostaining. Statistical analysis using Fisher's exact test revealed significant P-values for LC3A/B (P=0.048), AMBRA-1 (P=0.033), Ki-67 (P=0.048) and surgical treatment (P=0.048). Consequently, a negative prognostic role for these two ATGs may be hypothesized in the development of CHs., Competing Interests: No competing interests have been declared., (Copyright © 2024, Spandidos Publications.)

Little information from clinical trials is available regarding the efficacy of trastuzumab treatment in subcentimetric breast carcinomas (BCs). The aim of this study was to verify the existence of correlations between HER2 and hormone receptor status, Ki67 values, grade, histotype and node involvement in a cohort of pT1a,b BCs from an area not widely covered by screening campaigns. A total of 410 pT1a,b BC formalin-fixed paraffin-embedded samples collected from eight Sicilian Anatomo-Pathological Units (APUs) were classified according to the WHO classification and tumour grading was established. Estrogen and progesterone receptor status, Ki67 labelling index and HER2 status were available. Relationships between immunohistochemical data and clinicopathological characteristics were investigated using the Chi-square test; the cohort was analysed with respect to pT1a and pT1b BC as well as to node status. Ductal infiltrating carcinoma was the prevalent histotype in the pT1a and pT1b stages; G2 was a more common tumour grade, with a range between 64.6% and 70% of pT1a and pT1b, respectively. Taking into consideration the lymph node involvement of pT1a,b BC, only 17.1% cases were node-positive without a relevant difference between pT1a and pT1b. No significant differences between pT1a and pT1b BC cases emerged in relation to Ki67 LI, hormone receptors and HER2 status. T1a,b BC cases were stratified by node involvement and a significant relationship was observed with grade as well as with HER2 status. A significant relationship for pT1a cases emerged only for tumour grade, while pT1b cases showed a significant correlation exclusively with HER2 status. Our data clearly support the operative guidelines of the National Comprehensive Cancer Network. Therefore, the combined treatment with trastuzumab plus chemotherapy should be administered only to patients with pT1b or larger BCs. In small HER2-positive pT1a or microinvasive BC, this therapy should be considered on a case-by-case basis, considering tumour grade as the first characteristic.