Analysis of SLFN11 expression in small cell lung cancer, carcinoids and large cell neuroendocrine carcinoma: insights into lung neuroendocrine neoplasms.
SLFN11, highly expressed in SCLC, predicts sensitivity to DNA-damaging agents. Its role in other lung neuroendocrine neoplasms (NENs) (typical/atypical carcinoids - TC/AC and large cell neuroendocrine carcinoma- LCNEC) is unknown. This multicentre study assessed SLFN11 across lung NENs exploring its clinical-molecular associations.
SLFN11 immunohistochemistry (H-score 0-300) was assessed in 361 tumours (127 TC, 35 AC, 152 LCNEC, 47 SCLC). Ki67, pRb, cMYC, DLL3, ASCL1, HNF1a, OTP and NEUROD1, ASCL1, POU2F3, and YAP1 (NAPY; H-score > 50 as dominant subgroup) staining were integrated with clinicopathologic data and survival. Median SLFN11expression (exp) was used for survival analysis.
SLFN11exp varied across histologies (p < 0.001), with median values of 0 in TC (range 0-20) and AC (0-40), 2.49 (0-250) in LCNEC, 35 (0-240) in SCLC. SLFN11 showed a positive correlation with Ki67 (R2 = 0.187) across all histologies. In TC/AC, SLFN11exp was enriched in A1 subgroup tumours (known for ASCL1exp) (p = 0.035) and not correlated with OTP, HNF1A, CD44 and SSTR2Aexp. In LCNEC, SLFN11exp was higher in ASCL1high tumors (median 17.2; 0-162.5, p = 0.003) and correlated with cMYCexp (p = 0.024), but not with pRB and DLL3 status. In SCLC, a trend toward higher SLFN11exp in ASCL1high tumours was observed. SLFN11exp was not prognostic in TC/AC or LCNEC. In SCLC, SLFN11exp ≥ median value was associated with improved OS (13.9 vs 6.8 months; HR = 0.48, 95%CI 0.26-0.90, p = 0.020).
SLFN11exp in lung NENs is higher in SCLC > LCNEC > TC/AC, and correlated with Ki67. SLFN11exp was associated with ASCL1exp in all lung NENs. SLFN11 role in TC/AC and LCNEC remains to be defined.
SLFN11 immunohistochemistry (H-score 0-300) was assessed in 361 tumours (127 TC, 35 AC, 152 LCNEC, 47 SCLC). Ki67, pRb, cMYC, DLL3, ASCL1, HNF1a, OTP and NEUROD1, ASCL1, POU2F3, and YAP1 (NAPY; H-score > 50 as dominant subgroup) staining were integrated with clinicopathologic data and survival. Median SLFN11expression (exp) was used for survival analysis.
SLFN11exp varied across histologies (p < 0.001), with median values of 0 in TC (range 0-20) and AC (0-40), 2.49 (0-250) in LCNEC, 35 (0-240) in SCLC. SLFN11 showed a positive correlation with Ki67 (R2 = 0.187) across all histologies. In TC/AC, SLFN11exp was enriched in A1 subgroup tumours (known for ASCL1exp) (p = 0.035) and not correlated with OTP, HNF1A, CD44 and SSTR2Aexp. In LCNEC, SLFN11exp was higher in ASCL1high tumors (median 17.2; 0-162.5, p = 0.003) and correlated with cMYCexp (p = 0.024), but not with pRB and DLL3 status. In SCLC, a trend toward higher SLFN11exp in ASCL1high tumours was observed. SLFN11exp was not prognostic in TC/AC or LCNEC. In SCLC, SLFN11exp ≥ median value was associated with improved OS (13.9 vs 6.8 months; HR = 0.48, 95%CI 0.26-0.90, p = 0.020).
SLFN11exp in lung NENs is higher in SCLC > LCNEC > TC/AC, and correlated with Ki67. SLFN11exp was associated with ASCL1exp in all lung NENs. SLFN11 role in TC/AC and LCNEC remains to be defined.
Authors
Scattolin Scattolin, Heijboer Heijboer, Pigato Pigato, Derks Derks, Speel Speel, van Weert van Weert, Dumoulin Dumoulin, Domenico Domenico, Hillen Hillen, Guarneri Guarneri, Dingemans Dingemans, Pasello Pasello, von der Thüsen von der Thüsen
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