Ann Thorac Surg 2006;81:1988-1995
© 2006 The Society of Thoracic Surgeons
Original article: General thoracic
Prognostic Value of Histology in Resected Lung Cancer With Emphasis on the Relevance of the Adenocarcinoma Subtyping
Marc Riquet, MD, PhD
*
,
Christophe Foucault, MD,
Pascal Berna, MD,
Jalal Assouad, MD,
Antoine Dujon, MD,
Claire Danel, MD
a
,
b
a Service de Chirurgie Thoracique et d'Anatomie Pathologique, Hôpital Européen Georges Pompidou, Paris, France
b Centre Medico-Chirurgical du Cèdre, Boisguillaume, France
Accepted for publication January 4, 2006.
* Address correspondence to Dr Riquet, Service de Chirurgie Thoracique, Hôpital Européen Georges Pompidou, 20 rue Leblanc, 75908 Paris Cedex 15, France (Email: marc.riquet{at}hop.egp.ap-hop-paris.fr).
 |
Abstract
|
|---|
BACKGROUND: Adenocarcinoma (AC) is the most common lung cancer, followed by squamous cell carcinoma (SCC). Controversy exists concerning both cell types. Our purpose was to compare their prognosis after resection and determine whether AC subtyping may have any significance.
METHODS: From 1993 to 2002, 574 patients with SCC and 565 with AC underwent a curative resection and were compared according to sex, age, type of resection, TNM system classification, and survival. One hundred fifty-nine patients with ACs demonstrated a pure histologic pattern according to the 1999 World Health Organization classification, and 406 were of the mixed subtype including cell types with potentially different aggressiveness. Therefore, we compared subgroups according to presence or not of bronchioloalveolar carcinoma or solid adenocarcinoma with mucin component, or both.
RESULTS: Compared with ACs, SCCs had a higher number of males and older patients, and incidences of endobronchial tumors, pneumonectomies, and stage II tumors were higher. Global survival rates were not different. The ACs with solid AC with mucin components (n = 239) were characterized by more males and stage IIB patients, and had poorer survival rates (38.6% vs 61.4%; p < 0.0014) than the ACs without solid AC with mucin component. When comparing these with SCCs, 5-year survival rates were: ACs without solid AC with mucin component (58.1%), SCCs (50.2%), and ACs with solid AC with mucin component (36.8%) (p < 0.000019). Multivariate analysis demonstrated these subgroups and SCCs to be independent factors of prognosis.
CONCLUSIONS: Solid ACs with a mucin component demonstrated the poorest prognosis after resection. Further studies of this cell type, which should be looked for carefully, may help improve targetting adjuvant therapies.
|
Introduction
|
|---|
Lung cancer is the most frequent malignant neoplasm. The four main histopathologic types (squamous cell carcinomas [SCCs], adenocarcinomas [ACs], large cell undifferentiated carcinomas, and small cell undifferentiated carcinomas) account for more than 95% of diagnosed cases [1]. In contrast to generally declining squamous and small cell carcinoma rates among males, AC rates have risen in virtually all countries, with the increase exceeding 50%, and rates among females more than doubling in France [2]. A substantial amount of clinical and basic science research has focused on the prognostic factors for patients with lung cancer. The literature has grown rapidly and has identified more than 150 prognostic factors pertaining to the tumor, to the patient, or to the environment [3]. The survival of patients with nonsmall cell lung cancer who undergo a complete resection is closely correlated to the pathologic stage of disease [4]. Most studies generally comparing AC with SCC have not shown cell type to have independent prognostic value. However, some studies have concluded that AC has a negative impact on prognosis [3], whereas other more recent studies have reported that AC favorably influences the prognosis [5, 6].
Adenocarcinomas are highly and histologically heterogeneous, with only a minority of cases showing a pure histologic pattern [7]. Major new changes in the 1999 World Health Organization (WHO) classification include a strict definition of bronchoalveolar carcinomas (BACs) and the addition of a mixed type and several variant subtypes [7]. Bronchoalveolar carcinoma is the only subtype with a proven and more favorable prognosis [3, 7].
Subtypes of AC may influence prognosis; in 1978, Kemeny and colleagues [8] reported that patients with AC had a slightly poorer survival time than those with SCC but that this difference disappeared if all glandular cancers were analyzed as a group (ie, BACs and ACs). According to the 1999 WHO appraisal, further work is needed to better clarify the prognostic significance of AC subtyping based on cases studied with detailed histologic criteria. The purpose of our study was to compare the prognosis of both SCCs and ACs and attempt to determine how subtyping ACs may have significance.
|
Material and Methods
|
|---|
Patients
Between January 1, 1993 and December 31, 2002, 1,878 consecutive patients underwent surgical resection for nonsmall cell lung cancer at Georges Pompidou European Hospital and Boisguillaume Surgical Center. The surgical procedure was a potentially curative complete resection with systematic hilar and mediastinal lymphadenectomy. Patients who had preoperative neoadjuvant therapy or palliative surgery, and patients with prior history of malignancy had been excluded from this study. Of these 1,878 patients, 574 (30.6%) had SCC and 565 (30.1%) had AC, which represents 1,139 patients forming the basis of this study. There were 915 males and 224 females. Adjuvant therapy was performed in 358 patients in a nonrandomized fashion according to specific management adopted by the different referring physicians (251 patients received adjuvant radiation therapy and 107 received radiation and chemotherapy or chemotherapy alone). The cell type was not taken into consideration in the indication for adjuvant therapy. Our institutional review board waived obtaining patient consent for this study, and information was obtained from hospital case records.
Methods
Squamous cell carcinoma patients were compared with AC patients in terms of age, sex, type of resection performed, characteristics of the tumor, and staging, but also the details of the TNM system classification [4], in addition to survival with overall survival rates and survival rates according to staging. For regional lymph node (LN) involvement, we used the classification of Mountain and Dresler [9] as follows: the N1 population was further divided into intralobar levels (12 or 13) and interlobar, extralobar, or hilar levels (10 or 11); the N2 population was divided into single station N2, which is N2 involving superior mediastinal LN (2R + 4R or 3 or 4L) or aortic LN (5 or 6) or inferior mediastinal LN (7 or 8 or 9); and dual station N2, which is the involvement of any combination of two or more of the previously mentioned stations. The resected tumors were fixed routinely in 10% formalin, and selected samples of tumor were embedded in paraffin. All 4-µm sections of the tumor were stained by hematoxylin and eosin, periodic acid-Schiff with and without diastase digestion, and for immunochemistry with keratin antibodies. Adenocarcinoma was further classified according to the 1999 WHO proposals [7]. All surgical specimens of AC were reviewed by the same pathologist (CD). Of 565 ACs, 159 (28.1%) demonstrated a pure histologic pattern and 406 (71.9%) were of the mixed subtype.
The pure BAC component was observed in 15 patients. The BAC component was present as a mixed subtype in 120 patients. Among these patients, 24 had a BAC component predominant with a microinvasion, also classified by the WHO as "adenocarcinoma mixed bronchioloalveolar subtypes." This subgroup was studied separately. Pure histologic solid adenocarcinoma with mucin (SACM) was observed in 33 patients. The SACM component was present as mixed subtype in 206 patients, with 26 of them also having a BAC component.
According to the 1999 WHO appraisal, "tumor with a solid component will be poorly differenciated." Therefore, in the WHO classification, mixed subtype includes several different cell types of potentially variable aggressiveness. To determine whether subtyping may have an incidence on prognosis we distinguished subgroups among mixed subtypes according to presence or not of BAC or SACM components, or both. These subgroups were compared with each other and with SCCs in the same terms that the SCC group was compared with the AC group. Follow-up information was obtained either from hospital case records, or from a questionnaire completed by the local chest physician or general practitioner, or from death certificates.The overall survival was the main outcome, which was defined as the time interval between the surgery date and the date of death or the last follow-up. Actuarial survival curves were estimated by the Kaplan-Meier method. Statistical comparisons were made using the log-rank test. Univariate and multivariate analyses were performed using the Cox proportionnal hazards model. Univariate analyses used the following explanatory variables: gender, age, type of surgical resection, histologic cell type and subtype, T and N status, and the stage of disease. Hazard ratios with their 95% confident interval were estimated. The cut off p value used for entering specific explanatory variables into the multivariate analysis was 0.05. The p values were adjusted according to the multiplicity of tests using the Bonferroni method for all tests. All data analyses were conducted with the two-sided test. A p value less than 0.05 was considered statistically significant. The statistical software used for analysis was SEM (CAC J. Perrin, Clermont Ferrand, France) [10].
|
Results
|
|---|
Squamous cell carcinoma and AC patients presented significant differences (Table 1). The SCC group was observed to have more male patients, older patients, pneumonectomies and completion pneumonectomies, endobronchial tumors, larger sized tumors, more stage II and less stage I tumors than the AC group. Pathologic information is detailed in Table 2. Findings were more T3 tumors (due to bronchial involvement) and more N1 patients among SCCs, whereas AC patients demonstrated more T2 tumors, more visceral pleural involvement (VPI), more N0 and N2, more lymphatic invasion, and more associated nodules in homolateral lobes. The higher frequency of N2 in the AC group was due to a higher frequency of dual station involvement, and VPI and N2 involvement were correlated (N2 = 36.4%; 64 of 176 in cases of VPI vs N2 = 26.8%; 100 of 373). In cases without VPI the p value was 0.02, which was mainly due to dual station involvement of 15.9% (28 of 176) in cases of VPI versus 9.9% (37 of 373) in cases without VPI in which the p value was 0.04. However, overall long-term survival rates were the same between SCC and AC patients. Results were not modified by removing BAC from the AC.
View this table:
[in this window]
[in a new window]
|
Table 1. Main Characteristics of Squamous Cell Carcinomas, Adenocarcinomas, Solid Adenocarcinomas With Mucin Component, Bronchoalveolar Carcinoma With and Without Microinvasion Component
|
|
View this table:
[in this window]
[in a new window]
|
Table 2. Main Characteristics of Squamous Cell Carcinomas, Adenocarcinomas, Solid Adenocarcinomas With Mucin Component, Bronchoalveolar Carcinoma With and Without Microinvasion Component
|
|
The main characteristics of the AC subtypes are shown in Table 3. There were not many differences between these subgroups even when the BAC subtype with a microinvasive component was included in the mixed subtypes. However, there were more large sized (p = 0.018) and peripheral tumors in the BAC subtypes. The overall poorest long-term survival rates of pure histologic AC components were observed in acinar and SACM subtypes, respectively, 48.5 and 34.6%; the difference between both these poorest subtypes approached significance (p = 0.059). Mixed subtype subgroups according to presence or not of BAC or SACM components, or both, are shown in Table 4. The AC mixed subtypes classified in this manner consisted of seven subgroups: (1) AC mixed acinar and papillary subtype (n = 65; 11.5%); (2) AC mixed acinar or papillary and any variant (n = 17; 3%); (3) AC mixed acinar or papillary, or both, and BAC component more than 20% (n = 58; 10.3%); (4) AC mixed acinar or papillary, or both, and BAC component less than 20% (n = 36; 6.4%); (5) SACM mixed with acinar or papillary, or both, with or without variants component (n = 180; 31.9%); (6) SACM mixed with other components and BAC more than 20% (n = 13; 2.3%); (7) SACM mixed with other components and BAC less than 20% (n = 13; 2.3%).
View this table:
[in this window]
[in a new window]
|
Table 4. Characteristics of Mixed Subtypes According to Presence or Not of Bronchoalveolar Carcinoma Component Given in % and Solid Adenocarcinoma With Mucin Component; G1 to G7 Subgroups of Adenocarcinoma Mixed Subtypes Referring to Text
|
|
Poorest long-term survival rates were observed when the SACM component was present (Table 4). Consequently, AC with a pure histologic pattern (BAC excluded, n = 15) and mixed subtypes (BAC with a microinvasive component excluded, n = 24) were regrouped according to absence (287 patients) or presence (239 patients) of an SACM component.
Adenocarcinomas with an SACM component were significantly characterized by more male patients, more stage II (mainly stage IIB), more T3 tumor (mainly parietal T3), and more lymphatic invasion. Patient demographics, pathologic information, and stage classification are shown in Tables 1 and 2. Five-year survival rates were highly different 38.6 versus 61.4% (p < 0.00014) when the SACM component was observed. In contrast, 5-year survival rates were not significantly different between all the ACs with a pure histologic subtype, including pure SACMs (n = 144), and all the ACs with mixed subtypes including the SACM component (n = 382): 47.6% and 48.6%, respectively (p = 0.53), (ie, when the SACM component was not individualized as a subgroup).
Squamous cell carcinoma (n = 574) and AC (n = 565) 5-year survival rates were not different (50.2% and 49.7%, respectively; p = 08), and were not modified by staging (Table 5). Nevertheless, in pTNM subgroups, best survival differences approaching significance were observed for stage IB ACs (63% vs 54.1%; p = 0.08), stage IIB (T3 N0) ACs (54.5% vs 30.7%; p = 0.07) and stage IIA SCCs (64.8% vs 36.6%; p = 0.06). Survival rates were better in N0 AC patients (64.8% vs 56.3%; p = 0.026), and in contrast, survival rates were better in N1 and T1 SCC patients (57.9% vs 42.4 %; p = 0.046 and 68.8% vs 58.4%; p = 0.033, respectively). In cases of N1 patients, the difference was mainly due to extralobar and hilar subgroups (SCCs [53.4%] vs ACs [21.4%]; p = 0.020).
In considering the size of the tumor, a difference in survival rates was observed for 
3-cm tumors (SCCs [n = 166; 69.2%] vs ACs [n = 245; 57.2%], respectively; p = 0.016), which was mainly due to the associated N1 patients (SCCs [n = 33; 64.6%] vs ACs [n = 29; 37.5%]; p = 0.039).
Among AC patients, long-term 5-year survival rates were the highest in cases with BAC subtypes (70.3%). The difference observed in cases with BACs with a microinvasion and BACs without a microinvasion (61.7% vs 84.8%) was not significant (p = 0.096). The poorest long-term 5-year survival rates were observed when the SACM component was present (39.1% vs 58.1%; p = 0.00014, with postoperative mortality excluded) (Table 5); postoperative mortality was significantly higher in cases of the SACM component (5.9% vs 1.7%; p = 0.012) (Table 1). Differences in survival were highly significant only in stage I (Fig 2), and in cases of N0 and T1 patients: 50.5% vs 77.4% [p = 0. 000004]; 52.4% vs 75% [p = 0. 000071]; and 31% vs 79.3% [p = 0.000001], respectively. Better survival rates were also observed for 3-cm tumors (without the SACM component [n = 140;70.8%] with BAC being excluded [n = 15] vs tumors with the SACM component [n = 99; 36.6%]; p =0. 0000015), which was also significant in cases of N0 disease (82.8% vs 51.7%; p = 0.00001) and N1 disease (67.7% vs 15.2%; p = 0.018).
View larger version (26K):
[in this window]
[in a new window]
|
Fig 2. Overall survival: 5-year survival rates between squamous cell carcinoma (50.2%, curve 1), adenocarcinoma (AC) without solid adenocarcinoma with mucin (58.1%, curve 2) and AC with solid adenocarcinoma with mucin (36.8%, curve 3) were not changed when excluding postoperative deaths (52.2%, 59.1%, and 39.1%, respectively; p = 0.00014).
|
|
Adjuvant therapy did not change the findings when included in the analysis. Survival after adjuvant therapy was not different between SCCs and ACs and between tumors with the SACM component and tumors without the SACM component. The type of adjuvant therapy (ie, chemotherapy, radiotherapy, or both radiotherapy and chemotherapy) did not influence these results.
Squamous cell carcinoma survival rates were significantly better than AC rates when the SACM component was present (p = 0.0016), but were worse when the SACM was absent (p = 0.016) (Fig 1). Multivariate analysis demonstrated pT, pN, age, and histologic subtype were independent factors of prognosis (Table 6). Adenocarcinomas with the SACM component were associated with a higher risk of death compared with ACs without the SACM component (hazard ratio, 1.65).
View larger version (22K):
[in this window]
[in a new window]
|
Fig 1. The 5-year survival according to the presence of a solid AC with mucin component stratified by stage. Difference was significant in stage 1 (St 1): 76% versus 47.3%. A difference persisted in stage 2 (St 2) and stage 3 (St 3), but was gradually smaller and not significant (NS). (SACM = solid adenocarcinoma with mucin.)
|
|
|
Comment
|
|---|
In general, SCCs more frequently arise in the proximal bronchi, whereas ACs and their variants are more frequently peripherally located [11] as also observed in this study. This explains differences observed in pathologic features and staging. Squamous cell carcinomas are thus characterized by a larger size, more endobronchial locations, more N1 involvement, and hence more stage II tumors and then more patients who require pneumonectomies (44.8% vs 16.6%). On the other hand, ACs demonstrate a more aggressive tendency to disseminate such as VPI, lymphatic invasion, satellite tumor nodule within the same lung, and N2 metastases, with N2 representing 70.7% (164 of 232) of all LN metastases, and more especially involving several stations. Predominant mediastinal N2 involvement in ACs has been previously mentioned [12], but we have not found other similar results in the literature, and we have no explanation for this predominance. Besides the hypothesis that desquamating cells from VPI of ACs may involve mediastinal LN by diaphragm pleural lymph reabsorbtion [13], another hypothesis may be that the biological behavior of AC itself plays an important role in mediastinal lymphatic dissemination.
Despite such differences, the overall long-term 5-year survival rate was similar between both cell types, as also reported by many authors during the last 40 years [8, 12, 14–18]. Long-term 5-year survival rates were not modified by pathologic staging of the tumor, as already mentioned in tumors of stage I [19, 20], stages I and II [16], and stages I, II, and IIIA [21]. When a difference was demonstrated between cell type survival, SCC was most often reported as providing a better outcome, but in general the difference occurred in a particular stage or subgroup within one stage ie, in stage I [22], stage IA [23], and stage IB [24], and in stage II [25], stage IIB [21], and in stage IIIA of N2 groups [8, 26]. AC provides an overall best survival [6], or a best survival only in stage I [27]. The SCC long-term survival rate was better in cases of T1 tumors and N1 involvement, which was already indicated by Mountain [28] and Van Rens and colleagues [21] in the T2 N1 substage. This may denote a greater tendency of SCC to remain a local disease longer. In contrast, the AC long-term survival rate, which was better in cases of N0 patients, was similar to the SCC long-term survival rate in cases of N2, despite more dual station involvement, which demonstrates a different biological behavior of AC cell type. The pTNM classification fails to demonstrate these biological differences in which only pathologic studies could shed some light. Effectively, AC includes many cell types, and among them, BAC and SACM are particular components.
Bronchoalveolar carcinoma is the only subtype of AC with a substantially more favorable prognosis than the other subtypes, with survival rates varying from 81% [19] to 88% [27] to 100% [29]. Whatever the publications, the number of BACs remain small. The WHO proposal [7] reclassifies BAC as "adenocarcinoma, mixed type with bronchioloalveolar features" if "stromal, vascular or pleural invasion is seen." In these cases we observed that the prognosis was better than in AC mixed type (Table 3), and we suggest subclassifying it as an AC with a pure histologic pattern, acinar, or papillary pattern not being obviously present and sufficient to acertain a mixed pattern. In contrast, tumors with an SACM component, either pure or mixed, seem to have the poorest prognosis. In 259 consecutive patients with advanced disease, Sorensen and colleagues [30] analyzed the prognostic implication of histopathologic subtyping of pulmonary ACs according to the 1981 WHO classification. Bronchoalveolar carcinoma had the longest median duration of response to chemotherapy (47 weeks), time to progression (33 weeks), and median survival (40 weeks), whereas corresponding values for solid carcinoma with mucus formation, which first appeared in the classification were 8, 12, and 22 weeks, respectively. In a similar study in patients with surgically treated stage I or II AC of the lung, Sorensen and Olsen [31] reported that there were no significant differences among the overall survival curves of the histopathologic subtypes. However, when the survival figures were analyzed in more detail, the same differences among the subtypes were revealed (ie, patients with solid carcinoma with mucin formation had an unfavorable prognosis).
In the 1999 WHO classification, AC mixed subtype with or without an SACM component are considered as belonging to the same group, but nevertheless both groups seem to be separate on a prognosis point of view. When comparing AC with or without an SACM component, presentation was not very different between both groups, except for an important increased frequency of male, pStage IIB and operative mortality in cases with AC with an associated SACM component (Table 1). In detail, there was more parietal T3 involvement and peripheral lymphatic invasion (Table 2). The overall long-term survival rate was lower mainly due to a better survival rate of pStage I well-differentiated AC, especially in cases of N0, T1, and < 3-cm tumors. This suggests that the presence of an SACM component directly influences the prognosis. The reason why is not explained, and unlike with the disease stage, the prognostic significance of histologic cell type by itself after resection of lung cancer in not clear [17].
In conclusion, the behaviors of SCCs and ACs differ, which becomes clearer when subtyping ACs. The SACM component is an independent factor of prognosis. Further studies are needed to confirm and explain the behavior of this latter cell type. This component should be carefully researched and mentioned in pathology reports, and the mixed subtype group, including this histologic component should be separated for prognosis and therapeutic purposes.
|
References
|
|---|
- Hammar SP. Common neoplasmsIn: Dail DH, Hammar SP, editors. Pulmonary pathology. New York: Springer Verlag; 1994. pp. 1123-1278.
- Devesa SS, Bray F, Vizcaino AP, Pakin DM. International lung cancer trends by histologic type: male: female difference diminishing and adenocarcinomas rates rising Int J Cancer 2005;117:294-299.[Medline]
- Brundage MD, Davies D, Mackillop WJ. Prognostic factors in non-small cell lung cancera decade of progress. Chest 2002;122:1037-1057.[Medline]
- Mountain CF. Revisions in the international system for staging lung cancer Chest 1997;111:1710-1717.[Medline]
- Rena O, Papalia E, Ruffini E, et al. Stage I pure bronchioloalveolar carcinomarecurrences, survival and comparison with adenocarcinoma of the lung. Eur J Cardiothorac Surg 2003;23:409-414.[Abstract/Free Full Text]
- Okada M, Nishio W, Sakamoto T, et al. Evolution of surgical outcomes for non-small cell lung cancertime trends in 1,465 consecutive patients undergoing complete resection. Ann Thorac Surg 2004;77:1926-1931.[Abstract/Free Full Text]
- World Health Organization Histological typing of lung tumors. 3rd ed.. Geneva: WHO: Springer Verlag; 1999.
- Kemeny M, Block LK, Braun DW, Martini N. Results of surgical treatment of carcinoma of the lung by stage and cell type Surg Gynecol Obstet 1978;147:865-871.[Medline]
- Mountain CF, Dresler CM. Regional lymph node classification for lung cancer staging Chest 1997;111:1718-1723.[Medline]
- Kwiatkowski F. SEM (Statistiques, Epidemiologie, Medecine)un outil de gestion informatique et statistique adapté à la recherche en cancérologie. Bull Cancer 2000;87:715-721.[Medline]
- Maddaus MA, Gimberg RJ. Clinical features, diagnosis and staging of lung cancer in thoracic surgergyIn: Pearson FG, Cooper JD, Deslauriers J, et al. editors. 2nd ed.. Philadelphia: Churchill Livingstone; 2002. pp. 813-836.
- Paulson DL Reisch JS. Long-term survival after resection for bronchogenic carcinoma Ann Surg 1976;184:324-332.[Medline]
- Manac'h D, Riquet M, Medioni J, Le Pimpec Barthes F, Dujon A, Danel C. Visceral pleura invasion by non-small cell lung canceran underrated bad prognostic factor. Ann Thorac Surg 2001;71:1088-1093.[Abstract/Free Full Text]
- Higgins GA, Beebe GN. Bronchogenic carcinomafactors in survival. Arch Surg 1967;94:539-549.[Medline]
- Shields TW, Conn JH, Robinette CD. Relationship of cell type and lymph node metastasis to survival after resection of bronchial carcinoma Ann Thorac Surg 1975;20:501-510.[Abstract]
- Ludwig Lung Cancer Study Group Adverse effect of intrapleural corynebacterium parvum as adjuvant therapy in resected stage I and II non-small cell carcinoma of the lung J Thorac Cardiovasc Surg 1985;89:842-847.[Abstract]
- Kadri MA, Dusseck JE. Survival and prognosis following resection of primary non-small cell bronchogenic carcinoma Eur J Cardiothorac Surg 1991;5:132-136.[Abstract]
- Alkattan K, Sepsas E, Townsen ER, et al. Factors affecting long term survival following resection for lung cancer Thorax 1996;51:1266-1269.[Abstract/Free Full Text]
- Williams DE, Pairolero PC, Davis CS, et al. Survival of patients surgically treated for stage I lung cancer J Thorac Cardiovasc Surg 1981;82:70-76.[Abstract]
- Gail MH, Eagan KT, Feld R, et al. Pronostic factors in patients with resected stage I non-small cell lung cancer Cancer 1984;54:1802-1813.[Medline]
- Van Rens MTM, Brutel de la Riviere A, Elbers HRJ, Van Den Bosch JMM. Prognostic assessment of 2,361 patients who underwent pulmonary resection for non-small cell lung cancer stage I, II and IIIA Chest 2000;117:374-379.[Medline]
- Wu YC, Lin CFJ, Hsu NH, Huang BS, Huang MH, Wang LS. Long-term results of pathological stage I non-small cell lung cancervalidation of using the number of totally removed lymph nodes as a staging control. Eur J Cardiothorac Surg 2003;24:994-1001.[Abstract/Free Full Text]
- Read RC, Yoder G, Schaeffer RC. Survival after conservative resection for T1 N0 M0 non-small cell lung cancer Ann Thorac Surg 1990;49:391-400.[Abstract]
- Padilla J, Calvo V, Penalver JC, et al. Survival and risk model for stage IB non-small cell lung cancer Lung Cancer 2002;36:43-48.[Medline]
- Ichinose Y, Yano T, Asoh H, Yokoyama H, Hoshino I, Katsuda Y. Prognostic factors obtained by a pathologic examination in completely resected non-small cell lung canceran analysis in each pathologic stage. J Thorac Cardiovasc Surg 1995;110:601-605.[Abstract/Free Full Text]
- Kirsh MM, Sloan H. Mediastinal metastases in bronchogenic carcinomainfluence of postoperative irradiation, cell type and location. Ann Thorac Surg 1982;33:459-463.[Abstract]
- Rena O, Oliaro A, Cavallo A, et al. Stage I non-small cell lung carcinomareally an early stage?. Eur J Cardiothorac Surg 2002;21:514-519.[Abstract/Free Full Text]
- Mountain CF. Surgery for stage IIIa-N2 non-small cell lung cancer Cancer 1994;73:2589-2598.[Medline]
- Sakurai H, Dobashi Y, Mizutani E, et al. Bronchioloalveolar carcinoma of the lung 3 centimeters or less in diametera prognostic assessement. Ann Thorac Surg 2004;78:1728-1733.[Abstract/Free Full Text]
- Sorensen JB, Hirsch FR, Olsen J. The prognostic implication of histopathologic subtyping of pulmonary adenocarcinoma according to the classification of the World Health Organization. An analysis of 259 consecutive patients with advanced disease Cancer 1988;62:361-367.[Medline]
- Sorensen JB, Olsen J. Prognostic implications of histopathologic subtyping in patients with surgically treated stages I or II adenocarcinoma of the lung J Thorac Cardiovasc Surg 1989;97:245-251.[Abstract]
This article has been cited by other articles:
|
|
|
|
 
P. Saintigny, B. Besse, P. Callard, A.-C. Vergnaud, S. Czernichow, M. Colombat, P. Girard, P. Validire, J.-L. Breau, J.-F. Bernaudin, et al.
Erythropoietin and Erythropoietin Receptor Coexpression Is Associated with Poor Survival in Stage I Non Small Cell Lung Cancer
Clin. Cancer Res.,
August 15, 2007;
13(16):
4825 - 4831.
[Abstract]
[Full Text]
[PDF]
|
|
|
Top
Abstract
Introduction
