Evaluation of the new IASLC/ATS/ERS proposed classification of adenocarcinoma based on lepidic pattern in patients with pathological stage IA pulmonary adenocarcinoma.

BACKGROUND: The International association for the study of cancer (IASLC)/American thoracic society (ATS)/European respiratory society (ERS) has established a new subclassification of lung adenocarcinoma, especially for the lepidic pattern component, formerly called bronchioloalveolar adenocarcinoma (BAC). According to the new classification, BAC has been classified into the following 4 main subtypes: adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), invasive adenocarcinoma (IA), and variants of invasive adenocarcinoma (VIA). An observational study was conducted to validate this classification in patients with pathological stage IA pulmonary adenocarcinoma. PATIENTS AND METHODS: 147 patients treated for pathological stage IA lung adenocarcinoma by complete resection at Osaka University Medical Hospital from January 1993 to December 2002 were assessed. The tumor specimens of the cohort were classified into the 4 subgroups. In addition, these groups were compared for various prognostic factors. RESULTS: Adenocarcinoma in situ was observed in 30 patients, MIA in 8, IA in 104, and VIA in 5 patients, with 5-year survival rates of 100, 100, 85.5, and 60.0 %, respectively. The relationship between the histological classification and K-ras mutation was significant (p < 0.001), especially when comparing the VIA group with the others (p ≪ 0.001). Ki67-labeling indices were significantly different between the AIS and IA groups (p = 0.040). CONCLUSIONS: This study validated the proposed IASLC/ATS/ERS classification for pulmonary adenocarcinoma in patients with pathological stage IA pulmonary adenocarcinoma. The difference between AIS and IA may depend on the proliferation of the carcinoma. In addition, the difference between VIA and the other adenocarcinoma types may depend on genetic factors, especially K-ras mutations.

[The new classification of lung adenocarcinoma]. / Adenokarzinome der Lunge--die neue Klassifikation.

The new, interdisciplinary IASLC/ATS/ERS classification of lung adenocarcinoma has achieved a considerable impact since its publication in the year 2011. It separates tumours into preinvasive, minimally invasive and invasive subtypes. The preinvasive lesions atypical, adenomatous hyperplasia (AAH) and adenocarcinoma in situ (AIS) together with the minimally invasive adenocarcinoma (MIA), have an excellent prognosis after complete resection with 100 % survival. It enables a reproducible tumour grading by the determination of the predominant histological growth pattern which could be confirmed in several follow-up studies. Thereby the mixed subtype was eliminated which formerly represented about 80 % of all adenocarcinomas. Similarly, the terms bronchioloalveolar adenocarcinoma and bronchioloalveolar tumour growth were eliminated because they represented several distinct entities, specifically the in-situ lesions AAH and ACIS as well as the non-in-situ/invasive tumours like minimally invasive adenocarcinoma, lepidic predominant adenocarcinoma (LPA) and invasive mucinous adenocarcinoma (IMA). Although the classification is based on data from tumour resections it accommodates the fact that most tumours are diagnosed on biopsies and cytological specimens and includes recommendations for an efficient work-up to preserve tissue for molecular testing. Furthermore, the morphological analysis may provide hints for molecular changes including mutations with therapeutic relevance that may enable targeted molecular diagnostics. This review presents essentials facts of the new classification that will be part of the next WHO classification of lung tumors and its follow-up publications.

Well-differentiated adenocarcinoma-bronchioloalveolar carcinoma-in situ adenocarcinoma: a conundrum.

Over the last decade, considerable changes have been made to the classification of pulmonary adenocarcinoma, mainly with respect to the classification of small solitary tumors. The main goal seems to have been the identification of tumors that not only follow an indolent clinical course but that can also be treated more conservatively. Thus, the most important change to the classification of lung adenocarcinoma was proposed for a tumor no greater than 3.0 cm in size with a pure lepidic growth pattern and lacking stromal, vascular, or pleural invasion, which should now be categorized as in situ adenocarcinoma. At the same time, a category of minimally invasive adenocarcinoma was proposed for tumors with a predominantly lepidic growth pattern, <3 cm in size, and with <5 mm invasion in greatest dimension in any 1 focus. What is interesting about all these developments is the fact that all the publications on this issue have been presented under the terms of small adenocarcinomas or bronchioloalveolar carcinoma. Unfortunately, the literature reviews that have proposed the change in nomenclature to in situ adenocarcinoma have not offered a more in-depth assessment of these neoplasms. More recently, a publication of a large series of cases of small adenocarcinomas has offered a different view and underscored some of the important issues that need to be taken into account before a serious change in the nomenclature can be considered.

Clinical relevance of the new IASLC/ERS/ATS adenocarcinoma classification.

In 2011, recommendations for a multidisciplinary classification of lung adenocarcinoma were published under the auspices of the International Association for the Study of Lung Cancer, the American Thoracic Society and the European Respiratory Society. The review was considered necessary due to emerging data on the radiological features, genetics and therapeutic approaches to lung adenocarcinoma, all underpinned by expanding the knowledge of the pathology of this common tumour. The existing WHO classification of 2004 was not really fit for this multidisciplinary focus on the disease. This review describes the recommendations made on the reporting of surgically resected lung cancers according to their predominant pattern, and argues the case for replacing the term bronchioloalveolar carcinoma (WHO 1999 and 2004 definition) with adenocarcinoma in situ and for the introduction of minimally invasive adenocarcinoma. There is also a discussion of diagnosis of non-small-cell lung carcinomas in the small biopsy or cytology setting, a practice that was inadequately addressed in WHO 2004, yet this is much more relevant to most pathologists' daily practice because 85% or so of adenocarcinomas are never resected. Predictive immunohistochemistry, used correctly, can reduce non-specific diagnosis to less than 10% of the cases. Finally, there is an overview of the emerging data on therapeutically relevant lung adenocarcinoma genetics, considering targetable mutations that are now the focus of much activity. The clinical relevance of these changes is discussed.

Diagnosis of lung adenocarcinoma in resected specimens: implications of the 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification.

A new lung adenocarcinoma classification has been published by the International Association for the Study of Lung Cancer, the American Thoracic Society, and the European Respiratory Society. This new classification is needed to provide uniform terminology and diagnostic criteria, most especially for bronchioloalveolar carcinoma. It was developed by an international core panel of experts representing all 3 societies with oncologists/pulmonologists, pathologists, radiologists, molecular biologists, and thoracic surgeons.This summary focuses on the aspects of this classification that address resection specimens. The terms bronchioloalveolar carcinoma and mixed subtype adenocarcinoma are no longer used. For resection specimens, new concepts are introduced, such as adenocarcinoma in situ and minimally invasive adenocarcinoma for small solitary adenocarcinomas with either pure lepidic growth (adenocarcinoma in situ) and predominant lepidic growth with invasion of 5 mm or less (minimally invasive adenocarcinoma), to define the condition of patients who will have 100% or near 100% disease-specific survival, respectively, if they undergo complete lesion resection. Adenocarcinoma in situ and minimally invasive adenocarcinoma are usually nonmucinous, but rarely may be mucinous. Invasive adenocarcinomas are now classified by predominant pattern after using comprehensive histologic subtyping with lepidic (formerly most mixed subtype tumors with nonmucinous bronchioloalveolar carcinoma), acinar, papillary, and solid patterns; micropapillary is added as a new histologic subtype. Variants include invasive mucinous adenocarcinoma (formerly mucinous bronchioloalveolar carcinoma), colloid, fetal, and enteric adenocarcinoma.It is possible that this classification may impact the next revision of the TNM staging classification, with adjustment of the size T factor according to only the invasive component pathologically in adenocarcinomas with lepidic areas.

Global gene expression differentiating pure bronchioloalveolar carcinoma from adenocarcinoma with bronchioloalveolar carcinoma features.

OBJECTIVES: Pure bronchioloalveolar carcinoma (BAC) is considered the early stage of lung adenocarcinoma, and is even regarded as lung adenocarcinoma in situ. This study was designed to investigate the differences in the gene expression of pure BAC and that of adenocarcinoma with bronchioloalveolar features and explore the mechanism of BAC progression to adenocarcinoma with bronchioloalveolar features METHODS: Total RNA was extracted from 16 tissue specimens. Expression analysis was carried out using Agilent 4 × 44 k arrays. Gene ontology analysis was used to define pathways altered in bronchioloalveolar progression. Differentially expressed candidate genes were validated using quantitative real-time PCR. The statistical analysis was carried out according to the methods of the paired t-test. RESULTS: Adenocarcinoma with bronchioloalveolar features demonstrated an increased expression of 23 genes and reduced expression of 20 genes compared with BAC. These genes were considered candidate marker genes for tumour progression and metastasis. Genes overexpressed in adenocarcinoma with bronchioloalveolar features included fibroblast growth factor receptor 1, and CLDN18 (claudin 18), whereas those overexpressed in BAC included ataxia telangiectasia and Rad3 related (ataxia telangiectasia mutated and Rad3-related), and activating transcription factor 2. Mitogen-activated protein kinase (MAPK) pathway seemed dysregulated in adenocarcinoma with bronchioloalveolar features compared with pure BAC. CONCLUSIONS: Microarray-based expression profiling revealed interesting novel candidate genes in BAC and adenocarcinoma with bronchioloalveolar features. The MAPK pathway seemed dysregulated in adenocarcinoma with bronchioloalveolar features compared with the pure BAC pathway, which is worthy of being explored because it could partially explain the mechanism of the progression of BAC to adenocarcinoma with bronchioloalveolar features.

Prognostic impact of tumor size eliminating the ground glass opacity component: modified clinical T descriptors of the tumor, node, metastasis classification of lung cancer.

INTRODUCTION: The presence of ground glass opacity (GGO) on high-resolution computed tomography (HRCT) is well known to be pathologically closely associated with adenocarcinoma in situ. Recently, measuring the tumor diameter including areas of GGO on HRCT has been reported to possibly overestimate the T status. The purpose of this study was to evaluate the significance of the tumor size measured eliminating the area of GGO on HRCT as a prognostic factor and to propose a refined TNM classification based on modified T descriptors. METHODS: Four hundred seventy-five patients with clinical T1a-T2bN0M0 non-small-cell lung cancer underwent surgical resection. All tumors were reclassified based on the diameter measured eliminating the GGO area on HRCT according to the seventh TNM classification of lung cancer. We defined this new classification as modified T descriptors categorizing into five groups: mTis, mT1a, mT1b, mT2a, and mT2b. The overall survival rates of the patients in the current and modified staging groups were evaluated. RESULTS: The 5-year survival rates were 88% and 82% in the patients with T1a and T1b tumors and 90% and 75% in the patients with mT1a and mT1b tumors, respectively. The differences in the survival rate of the patients classified by using mT1a and the other modified T descriptors were more clearly separated statistically than those of the patients classified by using the current T1a and other T descriptors. CONCLUSION: The modified T descriptors of the tumor size measured eliminating the GGO component on HRCT more clearly classified the prognoses of patients with early lung cancer than did the current T classification.

'Bronchioloalveolar carcinoma': is the term really dead? A critical review of a new classification system for pulmonary adenocarcinomas.

'Bronchioloalveolar carcinoma' (BAC) is a designation that has been in use for over 50 years. Recently, the International Association for the Study of Lung Cancer, in association with the American Thoracic Society and the European Respiratory Society (IASLC/ATS/ERS) has recommended dropping the term altogether. It is argued that 'BAC' has no clear conceptual meaning, has been used in conjunction with invasive tumours of various types, and was applied to mucinous and non-mucinous tumours that are pathogenetically distinct. In addition to replacing 'BAC' with the standard pathological 'adenocarcinoma in situ', the IASLC/ATS/ERS panel also attempted to tackle the more substantial problem of standardising the terminology of lung adenocarcinomas that are not clearly invasive. By identifying 'minimally invasive adenocarcinomas' with <5 mm invasion, the IASLC/ATS/ERS has attempted to classify invasive tumours with little metastatic potential. Problems remaining with the new classification include use of the term 'lepidic predominant adenocarcinoma' (LPA), which replaces BAC with invasive components, and lack of clarity regarding what constitutes true invasion in well-differentiated lung adenocarcinomas. Specifically, the distinction between acinar growth pattern and in situ growth is not standardised. The basis for the new classification, as well as the plethora of previous attempts at classifying lung adenocarcinomas that are neither clearly invasive nor clearly in situ, are reviewed. Time will determine if the use of a 5 mm limit is workable or if the term 'LPA' has traction.

Impact of collection and storage of lung tumor tissue on whole genome expression profiling.

Gene expression profiling could assist in revealing biomarkers of lung cancer prognosis and progression. The handling of biological samples may strongly influence global gene expression, a fact that has not been addressed in many studies. We sought to investigate the changes in gene expression that may occur as a result of sample processing time and conditions. Using Illumina Human WG-6 arrays, we quantified gene expression in lung carcinoma samples from six patients obtained at chest opening before and immediately after lung resection with storage in RNAlater [T1a((CO)) and T1b((LR))], after receipt of the sample for histopathology, placed in RNAlater [T2a((HP))]; snap frozen [T2b((HP.SF))]; or snap frozen and stored for 1 week [T2c((HP.SFA))], as well as formalin-fixed, paraffin-embedded (FFPE) block samples. Sampling immediately after resection closely represented the tissue obtained in situ, with only 1% of genes differing more than twofold [T1a((CO)) versus T1b((LR))]. Delaying tissue harvest for an average of 30 minutes from the operating theater had a significant impact on gene expression, with approximately 25% of genes differing between T1a((CO)) and T2a((HP)). Many genes previously identified as lung cancer biomarkers were altered during this period. Examination of FFPE specimens showed minimal correlation with fresh samples. This study shows that tissue collection immediately after lung resection with conservation in RNAlater is an optimal strategy for gene expression profiling.

Assessment of invasion in lung adenocarcinoma classification, including adenocarcinoma in situ and minimally invasive adenocarcinoma.

Classification of adenocarcinoma has undergone recent evaluation to better align histological classification with clinical outcomes. One terminology, in particular, that of bronchioloalveolar carcinoma (BAC), has been debated for many decades. Although initial discussion surrounded the cell-of-origin of this tumor, more recent confusion has been generated from the use of this term both as a pattern of growth within an otherwise invasive adenocarcinoma and as a term for a pre-invasive tumor synonymous with adenocarcinoma in situ. As a result, adenocarcinomas with quite different radiology, gross morphology and metastatic potential have been associated with the BAC term. Focusing on invasion and using an illustrative case, we will explore the current recommendations that incorporate assessment of invasion to clarify the confusion caused by the different uses of the historical term 'BAC'.

Adenocarcinomas with prominent lepidic spread: retrospective review applying new classification of the American Thoracic Society.

BACKGROUND: Recently, a new classification of lung adenocarcinomas has been proposed for tumors with lepidic spread. The greatest diameter of the invasive component determines minimally invasive cancers, and the term bronchioloalveolar carcinoma is no longer used. METHODS: We retrospectively reviewed 87 resected adenocarcinomas of the lung; 30 tumors with lepidic growth and without high-grade invasive areas were identified, and the invasive component was measured morphometrically and categorized. A dimension of 5 mm was the cutoff for invasion. Regional lymph node involvement and short-term follow-up were compared among subtypes of these well-differentiated and moderately differentiated adenocarcinomas. RESULTS: There were 11 well-differentiated adenocarcinomas with lepidic growth: 3 adenocarcinomas in situ (nonmucinous) and 8 minimally invasive adenocarcinomas (MIAs) (4 mucinous and 4 nonmucinous). There were 19 invasive moderately differentiated adenocarcinomas with a prominent lepidic growth pattern (LPAs). The mean size of the 3 adenocarcinomas in situ cases was 0.9±0.7 mm; the total size of the 8 MIA cases was 1.4±1.8 cm and that of the 19 LPA cases was 3.2±2.1 cm. The invasive size of the MIA was 0.3±0.6 and that of the LPA was 2.2±0.3. The invasive pattern of the LPAs was papillary and acinar without desmoplasia (n=3) and acinar with desmoplasia (n=16). Seven of the invasive desmoplastic tumors showed complex single-cell invasion or lymphatic invasion. Identification of the transition from lepidic to invasive acinar was straightforward because of the presence of elastotic desmoplasia. The transition between complex acinar papillary invasion and lepidic growth was often difficult to discern. Lymph node metastases were present in 5 cases (26%), all in tumors with an acinar, desmoplastic invasive component of >1 cm, with areas of single-cell invasion. With follow-up, progressive nodal involvement or distant metastases occurred in 4 patients, all with complex invasive patterns; 3 with invasion >1 cm and 1 with lymphatic invasion in smaller invasive tumors. Recurrent lung nodules occurred in 5 patients, including 1 patient with MIA, 1 with nondesmoplastic invasion, 2 with desmoplastic invasion, and 1 with complex desmoplastic invasion. CONCLUSIONS: Approximately one third of lung adenocarcinomas have significant lepidic spread, and of these nearly one third are minimally invasive. Measurement of the invasive component may be difficult without elastotic desmoplasia. In this small series, lymph node and distant metastases occurred only in those with complex invasive patterns, but lung recurrence occurred in all subtypes, including MIAs.

Bronchioloalveolar differentiation in lung adenocarcinomas.

The goals of the study were to determine what percentage of neoplasms with a bronchioloalveolar (BAC) component were considered pure BAC by current World Health Organization (WHO) criteria. Next, we wanted to determine the number of mucinous BACs using histochemical staining with Alcian Blue PAS. Finally, we aimed to elucidate by immunohistochemistry the thyroid transcription factor-1 (TTF-1) frequency and cytokeratin 7 (CK7) expression, particularly in regard to the mucinous and non-mucinous subtypes of BAC tumors. We made a retrospective review of Hematoxylin and Eosin stained slides and classification of histologic grade, tumor subtype, and percentage of pure BAC pattern, with further characterization by histochemical staining for Alcian Blue PAS and Immunohistochemical staining for thyroid TTF-1 and CK7. Only 10 of 30 tumors examined could be classified as BAC by current strict WHO criteria. Nine cases were classified into non-mucinous and only one case was recognized as mucinous BAC, which showed positive staining for Alcian Blue PAS. TTF-1 positivity was in 100% of the non-mucinous BACs and complete absence of staining was in one case of mucinous BACs. CK7 expression in bronchioloalveolar carcinoma has demonstrated CK7 marked staining in 90% of non-mucinous BACs, also one case of mucinous BACs showed marked staining for TTF-1. BACs of mucinous morphology were notable for their conspicuous absence of TTF-1 immunoreactivity.

Does lung adenocarcinoma subtype predict patient survival?: A clinicopathologic study based on the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society international multidisciplinary lung adenocarcinoma classification.

INTRODUCTION: Lung adenocarcinoma is a heterogeneous group of tumors with a highly variable prognosis, not well predicted by the current pathologic classification system. The 2004 World Health Organization classification results in virtually all tumors encountered in clinical practice being allocated to the adenocarcinoma of mixed subtype category. A new classification developed by an international multidisciplinary expert panel sponsored by the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society, is based on histomorphologic subtype and has recently been validated in a North American series of 514 stage I lung adenocarcinomas. We investigated the relationship between the new classification and patient survival in a series of Australian patients with stages I, II, and III lung adenocarcinoma. METHODS: We identified 210 patients from a surgical database who underwent resection of lung adenocarcinoma from 1996 to 2009. Two pathologists, blinded to patient outcome, independently performed histopathologic subtyping according to the new classification. Kaplan-Meier curves were used to calculate 5-year survival for each separate histopathologic subtype/variant. Univariate and multivariate analyses were undertaken to control for validated prognostic factors. RESULTS: We confirmed that the new subtypes of adenocarcinoma in situ, minimally invasive adenocarcinoma and lepidic-predominant adenocarcinoma had a 5-year survival approaching 100%, whereas micropapillary-predominant and solid with mucin-predominant adenocarcinomas were associated with particularly poor survival. Papillary-predominant and acinar-predominant adenocarcinomas had an intermediate prognosis. This effect persisted after controlling for stage. CONCLUSIONS: Classification of lung adenocarcinoma according to the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification correlated with 5-year survival. These relationships persisted after controlling for known prognostic patient and tumor characteristics. The new classification has advantages not only for individual patient care but also for better selection and stratification for clinical trials and molecular studies.

Bronchioloalveolar carcinoma and the significance of invasion: predicting biologic behavior.

A resected adenocarcinoma illustrates challenges in diagnosing bronchioloalveolar carcinoma (BAC). Bronchioloalveolar carcinoma is defined by lack of invasion, something that may be difficult to assess in scars. Small (≤0.5 cm) invasive foci have little impact on the good prognosis associated with low-stage tumors. The term microinvasive adenocarcinoma or minimally invasive adenocarcinoma has been proposed for otherwise typical BACs and small invasive foci measuring 0.5 cm or less. Larger areas of invasion are associated with a more aggressive course and more reliably distinguish BAC from other variants of adenocarcinoma. Separating BAC from other forms of adenocarcinoma is important owing to differences in prognosis and emerging therapeutic strategies.

Clinical features of bronchioloalveolar carcinoma with new histologic and staging definitions.

INTRODUCTION: To assess clinical features of bronchioloalveolar carcinoma (BAC) based on the 1999 World Health Organization Classification ("pure BAC"), compare patients with pure BAC with patients previously diagnosed as BAC not meeting the 1999 definition, and compare survival changes of pure BAC based on the old and new (2009) staging systems. METHODS: A pulmonary pathologist reviewed each BAC tumor diagnosed between January 1, 1997, and December 31, 2007, identifying cases meeting the new criteria. Cases were restaged according to the seventh edition of the tumor, node, metastasis classification introduced in 2009. Patients with pure BAC were analyzed under both staging systems for changes in overall survival estimation. RESULTS: Of 338 total patients who were diagnosed with BAC, 117 were classified as pure and 221 were non-pure BAC. Seventy-eight of the 117 and 178 of the 221 had no other primary lung cancer. One-year and 5-year survival for the 78 patients with pure BAC were 94.8 and 83.5%, and for the 178 patients were 92.6 and 46.4%, respectively. Restaging for pure BAC cases resulted in nine of the 78 cases (12%) changing stage. Compared with the old staging, patients with advanced stage under the new stage had a worse 5-year survival (53% versus 45%), but no change was observed for stage IA. CONCLUSIONS: For patients with pure BAC, the new pathologic system favorably affects survival and the new staging system may more accurately reflect prognosis in advanced stage cancer. Our results have important implications for researchers, clinicians, and patients.

Carcinoma NOS is a common histologic diagnosis and is increasing in proportion among non-small cell lung cancer histologies.

BACKGROUND: Recent clinical trials have demonstrated differential survival benefit from chemotherapy regimens according to non-small cell lung cancer (NSCLC) histology. We investigated whether the distribution of carcinoma NOS (not otherwise specified) among NSCLC cases in California have changed over time and determined the prognostic significance of carcinoma NOS. METHODS: Retrospective population-based study of 175,298 NSCLC patients diagnosed histologically or cytologically from the statewide California Cancer Registry from 1989 to 2006. RESULTS: Carcinoma NOS accounted for 22.1% of all NSCLC patients, was the most commonly diagnosed cytologically (37.0%), and had the poorest 5-year survival estimates (5.8%) and median overall survival (OS, 5 months) among all NSCLC histologies. The proportion of carcinoma NOS had increased significantly from 1989 to 2006 in both males and females, in both histologically and cytologically diagnosed NSCLC, among all four major ethnicities (whites, African American, Hispanic, and Asian), among all age categories, and among all American Joint Committee on Cancer stages. The very elderly (80+ years) had the highest proportion of carcinoma NOS and cytologically diagnosed NSCLC regardless of period of diagnosis. Cytologically diagnosed NSCLC had significantly decreased OS than histologically diagnosed NSCLC (p < 0.0001). Cox proportional hazards regression analysis applied to stage 4 NSCLC patients indicated carcinoma NOS (vs. adenocarcinoma; hazard ratio 1.061, 95% confidence interval 1.039-1.083, p < 0.0001) and cytologically diagnosed NSCLC (versus histologically diagnosed NSCLC, hazard ratio 1.043, 95% confidence interval 1.024-1.062, p < 0.0001) were independent unfavorable prognostic factors for OS. CONCLUSIONS: Carcinoma NOS was a common histologic diagnosis, had been increasing over time among NSCLC, and carried an independent unfavorable prognosis among stage 4 NSCLC patients.

Analysis of the T descriptors and other prognosis factors in pathologic stage I non-small cell lung cancer in China.

BACKGROUND: The seventh edition of the tumor, node, metastasis Classification of Malignant Tumors is due to be published in 2009. The recommendations of International Association for the Study of Lung Cancer for changes to the T descriptors have been published. We combined this new parameter with other well-established prognostic factors and performed multivariate survival analyses to validate its value in Chinese stage I non-small cell lung cancer (NSCLC). METHODS: We try to validate the new staging project in 325 patients who underwent complete surgical resection for stage I NSCLC in Single Institution of Shanghai Chest Hospital from 1998 to 2003. Variables in the analysis included age, gender, performance status, history of smoking, pathologic type, type of resection (pneumonectomy, lobectomy, and bilobectomy), tumor size (greatest dimension of tumor), T-status (T1 or T2), type of lymph node resection (systematic mediastinal lymphadenectomy or mediastinal lymph node sampling), lymphovascular vessel invasion, and adjuvant chemotherapy. RESULTS: The 5-year overall survival (OS) of patients whose tumor measured no larger than 2 cm in largest diameter or larger than 2 cm but no larger than 3 cm were 75.49 and 74.58%, respectively. For those with tumors measured larger than 3 cm but smaller than 5 cm or larger than 5 cm but smaller than 7 cm were 60.87 and 55.63%. The 5-year OS of patients whose tumor measured larger than 7 cm was 46.15% (p = 0.025). The 5-year disease-free survival rates of patients whose tumor measured no larger than 2 cm in largest diameter or larger than 2 cm but no larger than 3 cm were 67.65 and 66.67%, respectively. For those with tumors measured larger than 3 cm but smaller than 5 cm or larger than 5 cm but smaller than 7 cm were 53.14 and 52.63%. The 5-year disease-free survival rate of patients whose tumor measured larger than 7 cm was 30.77% (p = 0.009). Multivariate analyses revealed that age, gender, type of resection (pneumonectomy, lobectomy, and bilobectomy), tumor size (greatest dimension of tumor), type of lymph node resection (systematic mediastinal lymphadenectomy or mediastinal lymph node sampling), and lymphovascular vessel invasion were significant predictive factors for OS. CONCLUSIONS: The tumor size is a significant independent prognostic factors in stage I NSCLC.