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Comparative profiling of surgically resected primary tumors and their lymph node metastases in small-cell lung cancer

K. Csende, B. Ferencz, K. Boettiger, MD. Pozonec, A. Lantos, A. Ferenczy, O. Pipek, A. Solta, B. Ernhofer, V. Laszlo, E. Megyesfalvi, K. Schelch, V. Pozonec, J. Skarda, V. Skopelidou, Z. Lohinai, C. Lang, L. Horvath, K. Dezso, J. Fillinger, F....

. 2025 ; 10 (4) : 104514. [pub] 20250318

Language English Country England, Great Britain

Document type Journal Article, Comparative Study

Persistent link   https://www.medvik.cz/link/bmc25016245

BACKGROUND: Profiling studies in small-cell lung cancer (SCLC) have mainly focused on primary tumors, omitting the potential molecular changes that might occur during lymphatic metastasis formation. Here, we assessed the molecular discordance between primary SCLCs and corresponding lymph node (LN) metastases in the light of subtype distribution and expression of clinically relevant proteins. METHODS: Comparative profiling of 32 surgically resected primary SCLCs and their LN metastases was achieved by RNA expression analysis and immunohistochemistry (IHC). In addition to subtype markers (ASCL1, NEUROD1, POU2F3, and YAP1), the expression of nine cancer-specific proteins was evaluated. RESULTS: The selected clinically relevant molecules showed no significant differences in their RNA expression profile when assessing the primary tumors and their corresponding LN metastases. Nevertheless, IHC analyses revealed significantly higher DLL3 expression in the primary tumors than in the LN metastases (P = 0.008). In contrast, NEUROD1 expression was significantly lower in the primary tumors (versus LN metastases, P < 0.001). No statistically significant difference was found by IHC analysis in the case of other clinically relevant proteins. Concerning SCLC molecular subtypes, a change in subtype distribution was detected in 21 cases. Phenotype switching from neuroendocrine (NE) subtypes toward non-NE lesions and from non-NE landscape toward NE subtypes were both detected. CONCLUSIONS: Although the molecular landscape of SCLC LN metastases largely resembles that of the tumor of origin, key differences exist in terms of DLL3 and NEUROD1 expression, and in subtype distribution. These diagnostic pitfalls should be considered when establishing the tumors' molecular profile for future clinical trials solely based on LN biopsies.

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$a Csende, K $u Department of Thoracic Surgery, Semmelweis University and National Institute of Oncology, Budapest, Hungary; National Koranyi Institute of Pulmonology, Budapest, Hungary
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$a Comparative profiling of surgically resected primary tumors and their lymph node metastases in small-cell lung cancer / $c K. Csende, B. Ferencz, K. Boettiger, MD. Pozonec, A. Lantos, A. Ferenczy, O. Pipek, A. Solta, B. Ernhofer, V. Laszlo, E. Megyesfalvi, K. Schelch, V. Pozonec, J. Skarda, V. Skopelidou, Z. Lohinai, C. Lang, L. Horvath, K. Dezso, J. Fillinger, F. Renyi-Vamos, C. Aigner, B. Dome, Z. Megyesfalvi
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$a BACKGROUND: Profiling studies in small-cell lung cancer (SCLC) have mainly focused on primary tumors, omitting the potential molecular changes that might occur during lymphatic metastasis formation. Here, we assessed the molecular discordance between primary SCLCs and corresponding lymph node (LN) metastases in the light of subtype distribution and expression of clinically relevant proteins. METHODS: Comparative profiling of 32 surgically resected primary SCLCs and their LN metastases was achieved by RNA expression analysis and immunohistochemistry (IHC). In addition to subtype markers (ASCL1, NEUROD1, POU2F3, and YAP1), the expression of nine cancer-specific proteins was evaluated. RESULTS: The selected clinically relevant molecules showed no significant differences in their RNA expression profile when assessing the primary tumors and their corresponding LN metastases. Nevertheless, IHC analyses revealed significantly higher DLL3 expression in the primary tumors than in the LN metastases (P = 0.008). In contrast, NEUROD1 expression was significantly lower in the primary tumors (versus LN metastases, P < 0.001). No statistically significant difference was found by IHC analysis in the case of other clinically relevant proteins. Concerning SCLC molecular subtypes, a change in subtype distribution was detected in 21 cases. Phenotype switching from neuroendocrine (NE) subtypes toward non-NE lesions and from non-NE landscape toward NE subtypes were both detected. CONCLUSIONS: Although the molecular landscape of SCLC LN metastases largely resembles that of the tumor of origin, key differences exist in terms of DLL3 and NEUROD1 expression, and in subtype distribution. These diagnostic pitfalls should be considered when establishing the tumors' molecular profile for future clinical trials solely based on LN biopsies.
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$a Ferencz, B $u Department of Thoracic Surgery, Semmelweis University and National Institute of Oncology, Budapest, Hungary; National Koranyi Institute of Pulmonology, Budapest, Hungary
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$a Boettiger, K $u Department of Thoracic Surgery, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
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$a Pozonec, M D $u Department of Thoracic Surgery, Semmelweis University and National Institute of Oncology, Budapest, Hungary; National Koranyi Institute of Pulmonology, Budapest, Hungary
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$a Lantos, A $u National Koranyi Institute of Pulmonology, Budapest, Hungary
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$a Ferenczy, A $u Department of Thoracic Surgery, Semmelweis University and National Institute of Oncology, Budapest, Hungary; Department of Obstetrics and Gynecology, South Buda Central Hospital, Saint Emeric University Teaching Hospital, Budapest, Hungary
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$a Pipek, O $u Department of Physics of Complex Systems, Eotvos Lorand University, Budapest, Hungary
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$a Solta, A $u Department of Thoracic Surgery, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
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$a Ernhofer, B $u Department of Thoracic Surgery, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
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$a Laszlo, V $u National Koranyi Institute of Pulmonology, Budapest, Hungary; Department of Thoracic Surgery, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
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$a Megyesfalvi, E $u Department of Thoracic Surgery, Semmelweis University and National Institute of Oncology, Budapest, Hungary; Department of Thoracic and Abdominal Tumors and Clinical Pharmacology, National Institute of Oncology, Budapest, Hungary
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$a Schelch, K $u Department of Thoracic Surgery, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
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$a Pozonec, V $u Department of Thoracic Surgery, Semmelweis University and National Institute of Oncology, Budapest, Hungary; Multidisciplinary Centre of Head and Neck Tumors, National Institute of Oncology, Budapest, Hungary
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$a Skarda, J $u Institute of Clinical and Molecular Pathology, Medical Faculty, Palacký University Olomouc, Olomouc, Czech Republic; Department of Pathology, University Hospital Ostrava, Ostrava, Czech Republic; Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic
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$a Skopelidou, V $u Department of Pathology, University Hospital Ostrava, Ostrava, Czech Republic; Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic
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$a Lohinai, Z $u Torokbalint County Institute of Pulmonology, Torokbalint, Hungary
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$a Lang, C $u Department of Thoracic Surgery, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Division of Pulmonology, Department of Medicine II, Medical University of Vienna, Vienna, Austria
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$a Horvath, L $u National Koranyi Institute of Pulmonology, Budapest, Hungary
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$a Dezso, K $u Department of Pathology and Experimental Cancer Research, Budapest, Hungary
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$a Fillinger, J $u National Koranyi Institute of Pulmonology, Budapest, Hungary
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$a Renyi-Vamos, F $u Department of Thoracic Surgery, Semmelweis University and National Institute of Oncology, Budapest, Hungary; National Koranyi Institute of Pulmonology, Budapest, Hungary; National Institute of Oncology and National Tumor Biology Laboratory, Budapest, Hungary
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$a Aigner, C $u Department of Thoracic Surgery, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
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$a Dome, B $u Department of Thoracic Surgery, Semmelweis University and National Institute of Oncology, Budapest, Hungary; National Koranyi Institute of Pulmonology, Budapest, Hungary; Department of Thoracic Surgery, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Translational Medicine, Lund University, Lund, Sweden. Electronic address: balazs.dome@meduniwien.ac.at
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$a Megyesfalvi, Z $u Department of Thoracic Surgery, Semmelweis University and National Institute of Oncology, Budapest, Hungary; National Koranyi Institute of Pulmonology, Budapest, Hungary; Department of Thoracic Surgery, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria. Electronic address: megyesfalvi.zsolt@semmelweis.hu
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