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Published in: Diagnostic Pathology 1/2015

Open Access 01-12-2015 | Research

Prognostic impact of vascular invasion and standardization of its evaluation in stage I non-small cell lung cancer

Authors: Rurika Hamanaka, Tomoyuki Yokose, Yuji Sakuma, Masahiro Tsuboi, Hiroyuki Ito, Haruhiko Nakayama, Kouzo Yamada, Ryota Masuda, Masayuki Iwazaki

Published in: Diagnostic Pathology | Issue 1/2015

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Abstract

Background

Patients with pathologic stage (p-Stage) IA non-small cell lung cancer (NSCLC) have a good survival rate because of possible curative resection. However, up to 10% of these patients relapse postoperatively. To identify unfavorable prognostic factors, we retrospectively analyzed the clinicopathological features of p-Stage IA disease, focusing on vascular invasion.

Methods

Of 467 patients with p-Stage I NSCLC, 335 were diagnosed with p-Stage IA or IB disease based on a lesion size ≤3 cm and the presence of pleural invasion (PL). Univariate and multivariate analyses of recurrence-free survival (RFS) were performed with age, sex, PL, and vascular invasion (blood vessel invasion [v] and lymphatic vessel invasion [ly]) as variables. To examine vascular invasion, hematoxylin-eosin (HE), Elastica van Gieson staining, and immunostaining with anti-podoplanin antibody were performed. The presence or absence of v and ly was recorded; the number of involved vessels was counted. Survival rates were obtained using the Kaplan–Meier method and log-rank test. Multivariate analyses were performed using the Cox proportional hazards model.

Results

RFS differed significantly between patients with no or one involved blood vessel (0 v or 1 v) and those with ≥2 involved vessels (≥2 v). Similarly, RFS differed significantly between patients with no lymphatic vessel involvement (0 ly) and those with one involved lymphatic vessel (1 ly). Thus, BVI(+) and BVI(−) were defined as ≥2 v and 0 v + 1 v, and LVI(+) and LVI(−) as ≥1 ly and 0 ly, respectively. BVI and LVI together represented tumor vessel invasion (TVI). On multivariate analyses, PL and TVI were independently associated with recurrence. Additionally, patients with p-Stage IA TVI(+) disease had a comparable recurrence rate to those with p-Stage IB disease.

Conclusions

Similar to PL, TVI is an important factor increasing the likelihood of recurrence. As HE staining alone is insufficient for evaluating vascular invasion, specific staining is necessary. Moreover, patients with p-Stage IA TVI(+) disease had a recurrence rate comparable to those with p-Stage IB disease; therefore, further studies should aim to elucidate whether patients with p-Stage IA TVI(+) disease should be administered postoperative chemotherapy similar to that received by p-Stage IB patients.

Virtual Slides

The virtual slide(s) for this article can be found here: http://​www.​diagnosticpathol​ogy.​diagnomx.​eu/​vs/​5213064891369688​
Literature
1.
go back to reference Visbal AL, Leighl NB, Feld R, Shepherd FA. Adjuvant chemotherapy for early-stage non-small cell lung cancer. Chest. 2005;128:2933–43.CrossRefPubMed Visbal AL, Leighl NB, Feld R, Shepherd FA. Adjuvant chemotherapy for early-stage non-small cell lung cancer. Chest. 2005;128:2933–43.CrossRefPubMed
2.
go back to reference Imaizumi M. Postoperative adjuvant cisplatin, vindesine, plus uracil-tegafur chemotherapy increased survival of patients with completely resected p-stage I non-small cell lung cancer. Lung Cancer. 2005;49:85–94.CrossRefPubMed Imaizumi M. Postoperative adjuvant cisplatin, vindesine, plus uracil-tegafur chemotherapy increased survival of patients with completely resected p-stage I non-small cell lung cancer. Lung Cancer. 2005;49:85–94.CrossRefPubMed
3.
go back to reference Roselli M, Mariotti S, Ferroni P, Laudisi A, Mineo D, Pompeo E, et al. Postsurgical chemotherapy in p-Stage IB nonsmall cell lung cancer: Long-term survival in a randomized study. Int J Cancer. 2006;119:955–60.CrossRefPubMed Roselli M, Mariotti S, Ferroni P, Laudisi A, Mineo D, Pompeo E, et al. Postsurgical chemotherapy in p-Stage IB nonsmall cell lung cancer: Long-term survival in a randomized study. Int J Cancer. 2006;119:955–60.CrossRefPubMed
4.
go back to reference Kato H, Ichinose Y, Ohta M, Hata E, Tsubota N, Tada H, et al. A randomized trial of adjuvant chemotherapy with uracil-tegafur for adenocarcinoma of the lung. N Engl J Med. 2004;350:1713–21.CrossRefPubMed Kato H, Ichinose Y, Ohta M, Hata E, Tsubota N, Tada H, et al. A randomized trial of adjuvant chemotherapy with uracil-tegafur for adenocarcinoma of the lung. N Engl J Med. 2004;350:1713–21.CrossRefPubMed
5.
go back to reference Kato H, Tsuboi M, Kato Y, Ikeda N, Okunaka T, Hamada C. Postoperative adjuvant therapy for completely resected early-Stage non-small cell lung cancer. Int J Clin Oncol. 2005;10:157–64.CrossRefPubMed Kato H, Tsuboi M, Kato Y, Ikeda N, Okunaka T, Hamada C. Postoperative adjuvant therapy for completely resected early-Stage non-small cell lung cancer. Int J Clin Oncol. 2005;10:157–64.CrossRefPubMed
6.
go back to reference Manac’h D, Riquet M, Medioni J, Le Pimpec-Barthes F, Dujon A, Danel C. Visceral pleura invasion by non-small cell lung cancer: an underrated bad prognostic factor. Ann Thorac Surg. 2001;71:1088–93.CrossRefPubMed Manac’h D, Riquet M, Medioni J, Le Pimpec-Barthes F, Dujon A, Danel C. Visceral pleura invasion by non-small cell lung cancer: an underrated bad prognostic factor. Ann Thorac Surg. 2001;71:1088–93.CrossRefPubMed
7.
go back to reference Kang JH, Kim KD, Chung KY. Prognostic value of visceral pleura invasion in non-small cell lung cancer. Eur J Cardiothorac Surg. 2003;23:865–9.CrossRefPubMed Kang JH, Kim KD, Chung KY. Prognostic value of visceral pleura invasion in non-small cell lung cancer. Eur J Cardiothorac Surg. 2003;23:865–9.CrossRefPubMed
8.
go back to reference Osaki T, Nagashima A, Yoshimatsu T, Yamada S, Yasumoto K. Visceral pleural involvement in non-small cell lung cancer: prognostic significance. Ann Thorac Surg. 2004;77:1769–73.CrossRefPubMed Osaki T, Nagashima A, Yoshimatsu T, Yamada S, Yasumoto K. Visceral pleural involvement in non-small cell lung cancer: prognostic significance. Ann Thorac Surg. 2004;77:1769–73.CrossRefPubMed
9.
go back to reference Shimizu K, Yoshida J, Nagai K, Nishimura M, Yokose T, Ishii G, et al. Visceral pleural invasion classification in non-small cell lung cancer: a proposal on the basis of outcome assessment. J Thorac Cardiovasc Surg. 2004;127:1574–8.CrossRefPubMed Shimizu K, Yoshida J, Nagai K, Nishimura M, Yokose T, Ishii G, et al. Visceral pleural invasion classification in non-small cell lung cancer: a proposal on the basis of outcome assessment. J Thorac Cardiovasc Surg. 2004;127:1574–8.CrossRefPubMed
10.
go back to reference Miyoshi K, Moriyama S, Kunitomo T, Nawa S. Prognostic impact of intratumoral vessel invasion in completely resected pathologic Stage I non-small cell lung cancer. J Thorac Cardiovasc Surg. 2009;137:429–34.CrossRefPubMed Miyoshi K, Moriyama S, Kunitomo T, Nawa S. Prognostic impact of intratumoral vessel invasion in completely resected pathologic Stage I non-small cell lung cancer. J Thorac Cardiovasc Surg. 2009;137:429–34.CrossRefPubMed
11.
go back to reference Fibla JJ, Cassivi SD, Brunelli A, Decker PA, Allen MS, Darling GE, et al. Re-evaluation of the prognostic value of visceral pleura invasion in Stage IB non-small cell lung cancer using the prospective multicenter ACOSOG Z0030 trial data set. Lung Cancer. 2012;78:259–62.CrossRefPubMed Fibla JJ, Cassivi SD, Brunelli A, Decker PA, Allen MS, Darling GE, et al. Re-evaluation of the prognostic value of visceral pleura invasion in Stage IB non-small cell lung cancer using the prospective multicenter ACOSOG Z0030 trial data set. Lung Cancer. 2012;78:259–62.CrossRefPubMed
12.
go back to reference Taube JM, Askin FB, Brock MV, Westra W. Impact of elastic staining on the staging of peripheral lung cancers. Am J Surg Pathol. 2007;31:953–6.CrossRefPubMed Taube JM, Askin FB, Brock MV, Westra W. Impact of elastic staining on the staging of peripheral lung cancers. Am J Surg Pathol. 2007;31:953–6.CrossRefPubMed
13.
go back to reference Travis WD, Brambilla E, Rami-Porta R, Vallières E, Tsuboi M, Rusch V, et al. International Staging Committee: Visceral pleural invasion: pathologic criteria and use of elastic stains: proposal for the 7th edition of the TNM classification for lung cancer. J Thoracic Oncol. 2008;3:1384–90.CrossRef Travis WD, Brambilla E, Rami-Porta R, Vallières E, Tsuboi M, Rusch V, et al. International Staging Committee: Visceral pleural invasion: pathologic criteria and use of elastic stains: proposal for the 7th edition of the TNM classification for lung cancer. J Thoracic Oncol. 2008;3:1384–90.CrossRef
14.
go back to reference Bréchot JM, Chevret S, Charpentier MC, Appere de Vecchi C, Capron F, Prudent J, et al. Blood vessel and lymphatic vessel invasion in resected nonsmall cell lung carcinoma. Correlation with TNM Stage and disease free and overall survival. Cancer. 1996;78:2111–8.CrossRefPubMed Bréchot JM, Chevret S, Charpentier MC, Appere de Vecchi C, Capron F, Prudent J, et al. Blood vessel and lymphatic vessel invasion in resected nonsmall cell lung carcinoma. Correlation with TNM Stage and disease free and overall survival. Cancer. 1996;78:2111–8.CrossRefPubMed
15.
go back to reference Okada M, Sakamoto T, Nishio W, Uchino K, Tsubota N. Characteristics and prognosis of patients after resection of nonsmall cell lung carcinoma measuring 2 cm or less in greatest dimension. Cancer. 2003;98:535–41.CrossRefPubMed Okada M, Sakamoto T, Nishio W, Uchino K, Tsubota N. Characteristics and prognosis of patients after resection of nonsmall cell lung carcinoma measuring 2 cm or less in greatest dimension. Cancer. 2003;98:535–41.CrossRefPubMed
16.
go back to reference Gabor S, Renner H, Popper H, Anegg U, Sankin O, Matzi V, et al. Invasion of blood vessel as significant prognostic factor in radically resected T1-3N0M0 non-small cell lung cancer. Eur J Cardiothorac Surg. 2004;25:439–42.CrossRefPubMed Gabor S, Renner H, Popper H, Anegg U, Sankin O, Matzi V, et al. Invasion of blood vessel as significant prognostic factor in radically resected T1-3N0M0 non-small cell lung cancer. Eur J Cardiothorac Surg. 2004;25:439–42.CrossRefPubMed
17.
go back to reference Tsuchiya T, Akamine S, Muraoka M, Kamohara R, Tsuji K, Urabe S, et al. Stage IA non-small cell lung cancer: vessel invasion is a poor prognostic factor and a new target of adjuvant chemotherapy. Lung Cancer. 2007;56:341–8.CrossRefPubMed Tsuchiya T, Akamine S, Muraoka M, Kamohara R, Tsuji K, Urabe S, et al. Stage IA non-small cell lung cancer: vessel invasion is a poor prognostic factor and a new target of adjuvant chemotherapy. Lung Cancer. 2007;56:341–8.CrossRefPubMed
18.
go back to reference Saijo T, Ishii G, Ochiai A, Hasebe T, Yoshida J, Nishimura M, et al. Evaluation of extratumoral lymphatic permeation in non-small cell lung cancer as a means of predicting outcome. Lung Cancer. 2007;55:61–6.CrossRefPubMed Saijo T, Ishii G, Ochiai A, Hasebe T, Yoshida J, Nishimura M, et al. Evaluation of extratumoral lymphatic permeation in non-small cell lung cancer as a means of predicting outcome. Lung Cancer. 2007;55:61–6.CrossRefPubMed
19.
go back to reference Shoji F, Haro A, Yoshida T, Ito K, Morodomi Y, Yano T, et al. Prognostic significance of intratumoral blood vessel invasion in pathologic Stage IA non-small cell lung cancer. Ann Thorac Surg. 2010;89:864–9.CrossRefPubMed Shoji F, Haro A, Yoshida T, Ito K, Morodomi Y, Yano T, et al. Prognostic significance of intratumoral blood vessel invasion in pathologic Stage IA non-small cell lung cancer. Ann Thorac Surg. 2010;89:864–9.CrossRefPubMed
20.
go back to reference Maeda R, Yoshida J, Ishii G, Hishida T, Nishimura M, Nagai K. Prognostic impact of intratumoral vascular invasion in non-small cell lung cancer patients. Thorax. 2010;65:1092–8.CrossRefPubMed Maeda R, Yoshida J, Ishii G, Hishida T, Nishimura M, Nagai K. Prognostic impact of intratumoral vascular invasion in non-small cell lung cancer patients. Thorax. 2010;65:1092–8.CrossRefPubMed
21.
go back to reference Ruffini E, Asioli S, Filosso PL, Buffoni L, Bruna MC, Mossetti C, et al. Significance of the presence of microscopic vascular invasion after complete resection of Stage I-II pT1–T2N0 non-small cell lung cancer and its relation with T-Size categories: did the 2009 7th edition of the TNM staging system miss something? J Thoracic Oncol. 2011;6:319–26.CrossRef Ruffini E, Asioli S, Filosso PL, Buffoni L, Bruna MC, Mossetti C, et al. Significance of the presence of microscopic vascular invasion after complete resection of Stage I-II pT1–T2N0 non-small cell lung cancer and its relation with T-Size categories: did the 2009 7th edition of the TNM staging system miss something? J Thoracic Oncol. 2011;6:319–26.CrossRef
22.
go back to reference Harada M, Hato T, Horio H. Intratumoral lymphatic vessel involvement is an invasive indicator of completely resected pathologic Stage I non-small cell lung cancer. J Thoracic Oncol. 2011;6:48–54.CrossRef Harada M, Hato T, Horio H. Intratumoral lymphatic vessel involvement is an invasive indicator of completely resected pathologic Stage I non-small cell lung cancer. J Thoracic Oncol. 2011;6:48–54.CrossRef
23.
go back to reference Shimada Y, Saji H, Yoshida K, Kakihana M, Honda H, Nomura M, et al. Pathological vascular invasion and tumor differentiation predict cancer recurrence in stage IA non–small cell lung cancer after complete surgical resection. J Thoracic Oncol. 2012;7:1263–70.CrossRef Shimada Y, Saji H, Yoshida K, Kakihana M, Honda H, Nomura M, et al. Pathological vascular invasion and tumor differentiation predict cancer recurrence in stage IA non–small cell lung cancer after complete surgical resection. J Thoracic Oncol. 2012;7:1263–70.CrossRef
24.
go back to reference Kaseda K, Ishii G, Aokage K, Takahashi A, Kuwata T, Hishida T, et al. Identification of intravascular tumor microenvironment features predicting the recurrence of pathological stage I lung adenocarcinoma. Cancer Sci. 2013;104:1262–9.CrossRefPubMed Kaseda K, Ishii G, Aokage K, Takahashi A, Kuwata T, Hishida T, et al. Identification of intravascular tumor microenvironment features predicting the recurrence of pathological stage I lung adenocarcinoma. Cancer Sci. 2013;104:1262–9.CrossRefPubMed
25.
go back to reference Kayser G, Baumhäkel JD, Szöke T, Trojan I, Riede U, Werner M, et al. Vascular diffusion density and survival of patients with primary lung carcinomas. Virchows Arch. 2003;442:462–7.PubMed Kayser G, Baumhäkel JD, Szöke T, Trojan I, Riede U, Werner M, et al. Vascular diffusion density and survival of patients with primary lung carcinomas. Virchows Arch. 2003;442:462–7.PubMed
26.
go back to reference Kayser K, Nwoye JO, Kosjerina Z, Goldmann T, Vollmer E, Kaltner H, et al. Atypical adenomatous hyperplasia of lung: its incidence and analysis of clinical, glycohistochemical and structural features including newly defined growth regulators and vascularization. Lung Cancer. 2003;42:171–82.CrossRefPubMed Kayser K, Nwoye JO, Kosjerina Z, Goldmann T, Vollmer E, Kaltner H, et al. Atypical adenomatous hyperplasia of lung: its incidence and analysis of clinical, glycohistochemical and structural features including newly defined growth regulators and vascularization. Lung Cancer. 2003;42:171–82.CrossRefPubMed
27.
go back to reference Szöke T, Kayser K, Trojan I, Kayser G, Furak J, Tiszlavicz L, et al. The role of microvascularization and growth/adhesion-regulatory lectins in the prognosis of non-small cell lung cancer in stage II. Eur J Cardiothorac Surg. 2007;31:783–7.CrossRefPubMed Szöke T, Kayser K, Trojan I, Kayser G, Furak J, Tiszlavicz L, et al. The role of microvascularization and growth/adhesion-regulatory lectins in the prognosis of non-small cell lung cancer in stage II. Eur J Cardiothorac Surg. 2007;31:783–7.CrossRefPubMed
Metadata
Title
Prognostic impact of vascular invasion and standardization of its evaluation in stage I non-small cell lung cancer
Authors
Rurika Hamanaka
Tomoyuki Yokose
Yuji Sakuma
Masahiro Tsuboi
Hiroyuki Ito
Haruhiko Nakayama
Kouzo Yamada
Ryota Masuda
Masayuki Iwazaki
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Diagnostic Pathology / Issue 1/2015
Electronic ISSN: 1746-1596
DOI
https://doi.org/10.1186/s13000-015-0249-5

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