Top

Published in:

01-04-2014 | Original Article

Lack of supportive evidence for the use of immunohistochemical staining to identify occult regional lymph node metastases in primary lung cancer

Authors: Per Jönsson, Leif Johansson, Maria Planck, Hans Brunnström

Published in: Virchows Archiv | Issue 4/2014

Abstract

Immunohistochemical (IHC) staining for the identification of nodal occult metastases (OM), not detected by routine histological examination, has been proposed for improved staging, prognostication and decision of adjuvant treatment in surgically treated primary lung cancer. In a prospective study, we analysed 178 cases of primary lung cancer stage I–III (N0-N1) for OM by immunostaining lymph node tissue using a broad-spectrum anti-cytokeratin antibody. OM were found in 7 (4 %) of the 178 cases. Using Kaplan-Meier analysis, overall survival was not significantly different between cases with stage I and cases upstaged to stage II because of OM (n = 3), or between cases with stage II and cases upstaged to stage III (n = 4). Likewise, the presence of OM was not significantly correlated with overall survival in univariable or multivariable Cox proportional hazards regression models, also when disregarding OM <0.2 mm in size. Given the low frequency of OM and lack of significant impact on survival in our study, the justification for including IHC staining of lymph nodes in lung cancer in clinical practise does not appear convincing. Moreover, we report several potential pitfalls in the use of broad-spectrum cytokeratin IHC staining for OM detection, for example staining of intra-nodal mesothelial cells.

Travis WD, Brambilla E, Müller-Hermelink HK, Harris CC (2004) World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Lung, Pleura, Thymus and Heart. IARC Press, Lyon. Available from: http://www.iarc.fr/en/publications/pdfs-online/pat-gen/bb10/index.php. Accessed 17 December 2013

National Board of Health and Welfare (2011) Official statistics of Sweden. Statistics—health and medical care. Causes of death 2010. The National Board of Health and Welfare, Stockholm. Available from: http://www.socialstyrelsen.se/publikationer2011/2011-7-6. [Accessed 17 December 2013]

Goldstraw P; International Association for the Study of Lung Cancer (IASLC) (2009) Staging manual in thoracic oncology. Editorial Rx Press, Orange Park

Sobin L, Gospodarowicz M, Wittekind C, International Union Against Cancer (UICC) (2009) TNM classification of malignant tumours, 7th edn. Wiley-Blackwell, Chichester

Lyman GH, Giuliano AE, Somerfield MR, Benson AB 3rd, Bodurka DC, Burstein HJ, American Society of Clinical Oncology et al (2005) American Society of Clinical Oncology guideline recommendations for sentinel lymph node biopsy in early-stage breast cancer. J Clin Oncol 23:7703–7720PubMedCrossRef

Herpel E, Muley T, Schneider T, Palm E, Kieslich de Hol D, Warth A et al (2010) A pragmatic approach to the diagnosis of nodal micrometastases in early stage non-small cell lung cancer. J Thorac Oncol 5:1206–1212PubMedCrossRef

Rusch VW, Hawes D, Decker PA, Martin SE, Abati A, Landreneau RJ et al (2011) Occult metastases in lymph nodes predict survival in resectable non-small-cell lung cancer: report of the ACOSOG Z0040 trial. J Clin Oncol 29:4313–4319PubMedCentralPubMedCrossRef

Vollmer RT, Herndon JE 2nd, D’Cunha J, Abraham NZ, Solberg J, Fatourechi M, Cancer and Leukemia Group B Trial 9761 et al (2003) Immunohistochemical detection of occult lymph node metastases in non-small cell lung cancer: anatomical pathology results from Cancer and Leukemia Group B Trial 9761. Clin Cancer Res 9:5630–5635PubMed

Marchevsky AM, Gupta R, Kusuanco D, Mirocha J, McKenna RJ Jr (2010) The presence of isolated tumor cells and micrometastases in the intrathoracic lymph nodes of patients with lung cancer is not associated with decreased survival. Hum Pathol 41:1536–1543PubMedCrossRef

10.

Passlick B, Izbicki JR, Kubuschok B, Nathrath W, Thetter O, Pichlmeier U et al (1994) Immunohistochemical assessment of individual tumor cells in lymph nodes of patients with non-small cell lung cancer. J Clin Oncol 12:1827–1832PubMed

11.

Brunnström H, Johansson L, Jirström K, Jönsson M, Jönsson P, Planck M (2013) Immunohistochemistry in differential diagnostics of primary lung cancer—an investigation within the Southern Swedish Lung Cancer Study. Am J Clin Pathol 140:37–46PubMedCrossRef

12.

Travis WD, Brambilla E, Noguchi M, Nicholson AG, Geisinger KR, Yatabe Y et al (2011) International association for the study of lung cancer/American thoracic society/European respiratory society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol 6:244–285PubMedCrossRef

13.

Chen ZL, Perez S, Holmes EC, Wang HJ, Coulson WF, Wen DR et al (1993) Frequency and distribution of occult micrometastases in lymph nodes of patients with non-small-cell lung carcinoma. J Natl Cancer Inst 85:493–498PubMedCrossRef

14.

Nicholson AG, Graham AN, Pezzella F, Agneta G, Goldstraw P, Pastorino U (1997) Does the use of immunohistochemistry to identify micrometastases provide useful information in the staging of node-negative non-small cell lung carcinomas? Lung Cancer 18:231–240PubMedCrossRef

15.

Maruyama R, Sugio K, Mitsudomi T, Saitoh G, Ishida T, Sugimachi K (1997) Relationship between early recurrence and micrometastases in the lymph nodes of patients with stage I non-small-cell lung cancer. J Thorac Cardiovasc Surg 114:535–543PubMedCrossRef

16.

Ohta Y, Nozawa H, Tanaka Y, Oda M, Watanabe Y (2000) Increased vascular endothelial growth factor and vascular endothelial growth factor-c and decreased nm23 expression associated with microdissemination in the lymph nodes in stage I non-small cell lung cancer. J Thorac Cardiovasc Surg 119:804–813PubMedCrossRef

17.

Hashimoto T, Kobayashi Y, Ishikawa Y, Tsuchiya S, Okumura S, Nakagawa K et al (2000) Prognostic value of genetically diagnosed lymph node micrometastasis in non-small cell lung carcinoma cases. Cancer Res 60:6472–6478PubMed

18.

Goldstein NS, Mani A, Chmielewski G, Welsh R, Pursel S (2000) Immunohistochemically detected micrometastases in peribronchial and mediastinal lymph nodes from patients with T1, N0, M0 pulmonary adenocarcinomas. Am J Surg Pathol 24:274–279PubMedCrossRef

19.

Wu J, Ohta Y, Minato H, Tsunezuka Y, Oda M, Watanabe Y et al (2001) Nodal occult metastasis in patients with peripheral lung adenocarcinoma of 2.0 cm or less in diameter. Ann Thorac Surg 71:1772–1777PubMedCrossRef

20.

Kawano R, Hata E, Ikeda S, Sakaguchi H (2002) Micrometastasis to lymph nodes in stage I left lung cancer patients. Ann Thorac Surg 73:1558–1562PubMedCrossRef

21.

Gu CD, Osaki T, Oyama T, Inoue M, Kodate M, Dobashi K et al (2002) Detection of micrometastatic tumor cells in pN0 lymph nodes of patients with completely resected non-small cell lung cancer: impact on recurrence and survival. Ann Surg 235:133–139PubMedCentralPubMedCrossRef

22.

Tezel C, Ersev AA, Kiral H, Urek S, Kosar A, Keles M et al (2006) The impact of immunohistochemical detection of positive lymph nodes in early stage lung cancer. Thorac Cardiovasc Surg 54:124–128PubMedCrossRef

23.

Brooks JS, LiVolsi VA, Pietra GG (1990) Mesothelial cell inclusions in mediastinal lymph nodes mimicking metastatic carcinoma. Am J Clin Pathol 93:741–748PubMed

24.

Parkash V, Vidwans M, Carter D (1999) Benign mesothelial cells in mediastinal lymph nodes. Am J Surg Pathol 23:1264–1269PubMedCrossRef

25.

Ludwig MS, Goodman M, Miller DL, Johnstone PA (2005) Postoperative survival and the number of lymph nodes sampled during resection of node-negative non-small cell lung cancer. Chest 128:1545–1550PubMedCrossRef

26.

Matsuguma H, Oki I, Nakahara R, Ohata N, Igarashi S, Mori K et al (2012) Proposal of new nodal classifications for non-small-cell lung cancer based on the number and ratio of metastatic lymph nodes. Eur J Cardiothorac Surg 41:19–24PubMedCentralPubMed

27.

Jonnalagadda S, Arcinega J, Smith C, Wisnivesky JP (2011) Validation of the lymph node ratio as a prognostic factor in patients with N1 nonsmall cell lung cancer. Cancer 117:4724–4731PubMedCentralPubMedCrossRef

28.

Qiu C, Dong W, Su B, Liu Q, Du J (2013) The prognostic value of ratio-based lymph node staging in resected non-small-cell lung cancer. J Thorac Oncol 8:429–435PubMedCrossRef

29.

Taghizadeh Kermani A, Bagheri R, Tehranian S, Shojaee P, Sadeghi RN, Krag D (2013) Accuracy of sentinel node biopsy in the staging of non-small cell lung carcinomas: systematic review and meta-analysis of the literature. Lung Cancer 80:5–14PubMedCrossRef

Title: Lack of supportive evidence for the use of immunohistochemical staining to identify occult regional lymph node metastases in primary lung cancer
Authors: Per Jönsson
Leif Johansson
Maria Planck
Hans Brunnström
Publication date: 01-04-2014
Publisher: Springer Berlin Heidelberg
Published in: Virchows Archiv / Issue 4/2014
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI: https://doi.org/10.1007/s00428-014-1558-x

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Lack of supportive evidence for the use of immunohistochemical staining to identify occult regional lymph node metastases in primary lung cancer

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 4/2014

Retroperitoneal dedifferentiated liposarcoma lacking MDM2 amplification in a patient with a germ line CHEK2 mutation

Gene expression profiling in patients with carcinoma of unknown primary site: from translational research to standard of care

microRNA expression might predict prognosis of epithelial hepatoblastoma

High GOLPH3 expression is associated with a more aggressive behavior of epithelial ovarian carcinoma

Reproducibility of histopathologic tumor grading in penile cancer—results of a European project

Multilayered epithelium at the gastroesophageal junction is a marker of gastroesophageal reflux disease: data from a prospective Central European multicenter study (histoGERD trial)