Abstract
BACKGROUND. Approximately 10-20% of nonsmall cell lung carcinomas (NSCLC) show neuroendocrine (NE) differentiation, as evaluated by panendocrine markers or ultrastructural evidence of dense-core secretory granules. However, little is known regarding the prevalence and clinical implications of NE differentiation in patients with Stage I NSCLC. METHODS. The authors analyzed 220 consecutive patients with Stage I NSCLC (pT1-T2N0M0) among 2100 patients with primary lung carcinoma who underwent surgical treatment between 1987 and 1993. Using light microscopy and immunohistochemical staining for synaptophysin, chromogranin A, and respiratory tract-related hormones, 28 NSCLC specimens with NE differentiation (NSCLC-ND) and 11 large cell neuroendocrine carcinoma (LCNEC) specimens were identified. RESULTS. The 28 NSCLC-ND specimens included 15 adenocarcinomas and 13 squamous cell carcinomas. Neoplastic cells with NE features never exceeded 20% in NSCLC-ND specimens, whereas neoplastic cells amounted to 20-90% in LCNEC specimens. NSCLC-ND specimens with > 5% NE -differentiated tumor cells showed increased Ki-67 labeling index (P = 0.007) and invasive phenotype, as evaluated by fascin immunoreactivity (P = 0.021). Patients with adenocarcinoma, but not with squamous cell carcinoma, who had > 5% NE-differentiated cells had a worse clinical course compared with patients who had ordinary NSCLC, with reduced overall survival (P = 0.017) and disease free survival (P = 0.049). In multivariate analysis, NE differentiation > 5% neoplastic cells in patients with adenocarcinoma independently predicted a poorer prognosis (hazard ratio, 2.61; 95% confidence interval, 0.99-6.85). Hormone production was restricted to chromogranin positive NSCLC-ND but did not affect prognosis. CONCLUSIONS. Stage I adenocarcinomas with ≥ 5% NE tumor cells are clinically aggressive tumors, similar to LCNEC. Hormone production identifies a more fully developed neuroendocrine phenotype but is not relevant to prognosis. The identification of NE- differentiated cells in patients with NSCLC may have clinical relevance.
| Original language | English |
|---|---|
| Pages (from-to) | 2487-2497 |
| Number of pages | 11 |
| Journal | Cancer |
| Volume | 97 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - May 15 2003 |
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Keywords
- Chromogranin A
- Hormone
- Immunohistochemistry
- Neuroendocrine differentiation
- Nonsmall cell lung carcinoma
- Survival
- Synaptophysin
ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Prognostic implications of neuroendocrine differentiation and hormone production in patients with stage I nonsmall cell lung carcinoma. / Pelosi, Giuseppe; Pasini, Felice; Sonzogni, Angelica; Maffini, Fausto; Maisonneuve, Patrick; Iannucci, Antonio; Terzi, Alberto; De Manzoni, Giovanni; Bresaola, Enrica; Viale, Giuseppe.
In: Cancer, Vol. 97, No. 10, 15.05.2003, p. 2487-2497.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Prognostic implications of neuroendocrine differentiation and hormone production in patients with stage I nonsmall cell lung carcinoma
AU - Pelosi, Giuseppe
AU - Pasini, Felice
AU - Sonzogni, Angelica
AU - Maffini, Fausto
AU - Maisonneuve, Patrick
AU - Iannucci, Antonio
AU - Terzi, Alberto
AU - De Manzoni, Giovanni
AU - Bresaola, Enrica
AU - Viale, Giuseppe
PY - 2003/5/15
Y1 - 2003/5/15
N2 - BACKGROUND. Approximately 10-20% of nonsmall cell lung carcinomas (NSCLC) show neuroendocrine (NE) differentiation, as evaluated by panendocrine markers or ultrastructural evidence of dense-core secretory granules. However, little is known regarding the prevalence and clinical implications of NE differentiation in patients with Stage I NSCLC. METHODS. The authors analyzed 220 consecutive patients with Stage I NSCLC (pT1-T2N0M0) among 2100 patients with primary lung carcinoma who underwent surgical treatment between 1987 and 1993. Using light microscopy and immunohistochemical staining for synaptophysin, chromogranin A, and respiratory tract-related hormones, 28 NSCLC specimens with NE differentiation (NSCLC-ND) and 11 large cell neuroendocrine carcinoma (LCNEC) specimens were identified. RESULTS. The 28 NSCLC-ND specimens included 15 adenocarcinomas and 13 squamous cell carcinomas. Neoplastic cells with NE features never exceeded 20% in NSCLC-ND specimens, whereas neoplastic cells amounted to 20-90% in LCNEC specimens. NSCLC-ND specimens with > 5% NE -differentiated tumor cells showed increased Ki-67 labeling index (P = 0.007) and invasive phenotype, as evaluated by fascin immunoreactivity (P = 0.021). Patients with adenocarcinoma, but not with squamous cell carcinoma, who had > 5% NE-differentiated cells had a worse clinical course compared with patients who had ordinary NSCLC, with reduced overall survival (P = 0.017) and disease free survival (P = 0.049). In multivariate analysis, NE differentiation > 5% neoplastic cells in patients with adenocarcinoma independently predicted a poorer prognosis (hazard ratio, 2.61; 95% confidence interval, 0.99-6.85). Hormone production was restricted to chromogranin positive NSCLC-ND but did not affect prognosis. CONCLUSIONS. Stage I adenocarcinomas with ≥ 5% NE tumor cells are clinically aggressive tumors, similar to LCNEC. Hormone production identifies a more fully developed neuroendocrine phenotype but is not relevant to prognosis. The identification of NE- differentiated cells in patients with NSCLC may have clinical relevance.
AB - BACKGROUND. Approximately 10-20% of nonsmall cell lung carcinomas (NSCLC) show neuroendocrine (NE) differentiation, as evaluated by panendocrine markers or ultrastructural evidence of dense-core secretory granules. However, little is known regarding the prevalence and clinical implications of NE differentiation in patients with Stage I NSCLC. METHODS. The authors analyzed 220 consecutive patients with Stage I NSCLC (pT1-T2N0M0) among 2100 patients with primary lung carcinoma who underwent surgical treatment between 1987 and 1993. Using light microscopy and immunohistochemical staining for synaptophysin, chromogranin A, and respiratory tract-related hormones, 28 NSCLC specimens with NE differentiation (NSCLC-ND) and 11 large cell neuroendocrine carcinoma (LCNEC) specimens were identified. RESULTS. The 28 NSCLC-ND specimens included 15 adenocarcinomas and 13 squamous cell carcinomas. Neoplastic cells with NE features never exceeded 20% in NSCLC-ND specimens, whereas neoplastic cells amounted to 20-90% in LCNEC specimens. NSCLC-ND specimens with > 5% NE -differentiated tumor cells showed increased Ki-67 labeling index (P = 0.007) and invasive phenotype, as evaluated by fascin immunoreactivity (P = 0.021). Patients with adenocarcinoma, but not with squamous cell carcinoma, who had > 5% NE-differentiated cells had a worse clinical course compared with patients who had ordinary NSCLC, with reduced overall survival (P = 0.017) and disease free survival (P = 0.049). In multivariate analysis, NE differentiation > 5% neoplastic cells in patients with adenocarcinoma independently predicted a poorer prognosis (hazard ratio, 2.61; 95% confidence interval, 0.99-6.85). Hormone production was restricted to chromogranin positive NSCLC-ND but did not affect prognosis. CONCLUSIONS. Stage I adenocarcinomas with ≥ 5% NE tumor cells are clinically aggressive tumors, similar to LCNEC. Hormone production identifies a more fully developed neuroendocrine phenotype but is not relevant to prognosis. The identification of NE- differentiated cells in patients with NSCLC may have clinical relevance.
KW - Chromogranin A
KW - Hormone
KW - Immunohistochemistry
KW - Neuroendocrine differentiation
KW - Nonsmall cell lung carcinoma
KW - Survival
KW - Synaptophysin
UR - http://www.scopus.com/inward/record.url?scp=0038370938&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0038370938&partnerID=8YFLogxK
U2 - 10.1002/cncr.11376
DO - 10.1002/cncr.11376
M3 - Article
C2 - 12733148
AN - SCOPUS:0038370938
VL - 97
SP - 2487
EP - 2497
JO - Cancer
JF - Cancer
SN - 0008-543X
IS - 10
ER -