Chinese-German Journal of Clinical Oncology
January 2010, Vol. 9, No. 1, P13–P16
DOI 10.1007/s10330-009-0180-x
Comparative analysis of lung cancer with features of bronchioloalveolar carcinoma and other types of adenocarcinoma* Leina Sun, Yan Guo, Zhongli Zhan, Baocun Sun, Na Dong, Ankang Gu, Huanling Luan Department of Pathology, Tianjin Medical Universit Cancer Institute and Hoapital, Tianjin Key Laboratory of Cancer Prevention; Tianjin Diagnosis and Therapy Cancer of Lung Cancer, Tianjin 300060, China Received: 29 October 2009 / Revised: 5 December 2009 / Accepted: 25 December 2009 © Springer-Verlag Berlin Heidelberg 2010 Abstract Objective: The aim of this study was to investigate the clinicopathologic and prognostic factors of the partial subtypes of lung adenocarcinoma, including pure bronchioloalveolar carcinoma (BAC), adenocarcinoma (AC) with BAC component and AC without BAC component. Methods: One hundred and six adenocarcinoma specimens which were followed up completely for 3 years, were obtained from 106 patients (45 men and 61 women) who underwent surgical resection for pathologically confirmed pulmonary adenocarcinoma in the Cancer Hospital of Tianjin Medical University, from June 2004 to December 2005. According to the recent 2004 World Health Organization (WHO) pathological classification criteria of lung cancer, lung adenocarcinomas were divided into three subgroups: pure BAC, AC with BAC component and AC without BAC component. The clinical data were retrospectively analyzed based on statistical methods. All data were analyzed using SPSS statistics software and Kaplan-Meier survival curves were constructed, meanwhile, we conducted a Log-rank test. Results: The statistical analysis showed that no significant association was found among the three groups in gender and age; however, smoke index, tumor size, N stage, TNM stage, postoperative recurrence and metastasis had a statistically significant correlation among three groups (P < 0.01). The 3-year survival rates of the three groups were 96.4%, 61.0% and 40.5% respectively, which had a statistically significant difference. And the 3-year survival rate was significantly higher in the patients with pure BAC than in the patients with other types of lung adenocarcinomas (P < 0.01). In contrast to the other two groups (pure BAC and AC with BAC component), we found the evidence that the 3-year prognosis of lung adenocarcinoma without BAC component was worse than the two formers. Conclusion: The three groups (pure BAC, AC with BAC component and AC without BAC component) have their own distinct clinicopathologic features respectively and completely different clinical prognosis. The strict distinction of the subtypes of lung adenocarcinoma can provide more reliable basis for scientific and comprehensive clinical treatment and contribute to assess the clinical prognosis effectively. Key words
lung cancer; adenocarcinoma (AC); bronchiolo-alveolar carcinoma (BAC); prognosis
The incidence of lung adenocarcinoma is showing a rising trend transparently. At present, it already has been the most frequent histological type of lung cancer in many countries. Its morphological heterogeneity is very common which often mixed with different types of component. Pure BAC accounts for non-small cell lung cancer (NSCLC) 2%–5%, but AC with BAC component in NSCLC is up to 20%. Because of its individuality of molecular biology, pathology, radiology, treatment and so on, BAC has been focus on by lots of researchers. In recent years, it has been shown that the biological characteristics of BAC is different from other types, which is
better than the laters [1]. It was rarely reported that the differences between pure BAC and AC with or without BAC component. We collected clinical information of patients with lung adenocarcinoma who underwent surgical resection and classified them into three groups: pure BAC, adenocarcinoma with BAC component and adenocarcinoma without BAC component based on the 2004 World Health Organization (WHO) classification. Then we make a retrospective analysis about their clinicopathologic significance.
Correspondence to: Zhongli Zhan. Email:
[email protected] * Supported by a grant from the National Nature Sciences Foundation of China (No. 30770828).
Patients and tumors Tumor samples from patients with primary lung adenocarcinoma were obtained from 106 randomly selected
Materials and methods
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Fig. 1 Bronchioloalveolar carcinoma, non-mucinous subtype (HE × 100)
Fig. 4 Adenocarcinoma, acinar subtype (HE × 200)
Fig. 2
Fig. 5 Survival curves of patients with different subtypes of adenocarcinoma
Bronchioloalveolar carcinoma, mucinous subtype (HE × 100)
(pure BAC; Fig. 1 and 2), group 2 (adenocarcinoma with BAC component; Fig. 3), and group 3 (invasive adenocarcinoma without BAC component; Fig. 4).
Fig. 3 100)
Mixed types of adenocarcinoma with a BAC component (HE ×
patients with lung cancer who were diagnosed at Cancer institute and Hospital of Tianjin Medical University from January 2004 to December 2005. Pathologic diagnosis All tissue slides, including the tumors and the corresponding lymph node slides, were read by two experienced pathology doctors according to the strict pathological diagnosis standard. Based on the 2004 WHO classification we divided them into three groups: group 1
Clinical materials Among the total of 106 patients, male patients accounted for 42.5% (45/106) and female accounted for 57.5% (61/106). They were between 36–78 years old, the mean age was 61 years old; 43 patients with metastasis of lymphonode (40.6%) and 63 without metastasis of lymphonode (59.4%). Group 1 has 28 examples, group 2 has 41 and group 3 has 37. Clinical information, including gender, age at diagnosis, and smoking history, were obtained by a retrospective review of the medical history recorded in the patients’ charts. Follow-up The patients were followed up from the surgery date to the death or the last revisit, taking the month as the unit. The revisit time was full of 3 years. Statistical analysis All analyses were performed using SPSS for Windows, version 13.0 (SPSS Inc., Chicago). Two-sided P values < 0.05 were considered significant.
Chinese-German J Clin Oncol, January 2010, Vol. 9, No. 1 Table 1
Clinical analysis of the subtypes of adenocarcinoma
Factors
Group 1 Group 2 Group 3
Sex Male Female Age (years) ≥ 60 < 60 Smoking indexes ≥ 400 < 400
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χ2
P
14 14
12 29
19 18
4.769
0.092
15 13
24 17
20 17
0.226
0.893
7 21
7 34
21 16
14.955 ǂ
0.001 ǂ
Table 2 The relationship between the subtype and pStage Factors Tumor diameter (cm) >3 ≤3 N factor N0 + N1 N2 pStage (piece/year) I + II III
Group 1 Group 2 Group 3
χ2
P
6 22
18 23
21 16
8.200
0.017
28 0
23 18
17 20
22.135
0.0
28 0
22 19
16 21
23.959 ǂ
0.0 ǂ
Table 3 The relationship between the subtype and postoperative recurrence Histological type Group 1 Group 2 Group 3
Postoperative recurrence Yes No 1 27 8 33 17 20
Total 28 41 37
Results General situation The statistical analysis showed that there was no significant difference in gender and age among the three groups; however, smoking index was statistically different among three groups (Table 1). Comparing two groups of the three groups optionally, we found a significant difference between group 1 and group 3 as well as group 2 and group 3, but not between group 1 and group 3 (P < 0.01). These data have been used to imply that pure BAC and adenocarcinoma with components of BAC could not have a strong relationship to cigarette exposure. Associations between subtype and pStage Tumor diameters, N stage and pStage were all significantly different among the three groups (Table 2). And the data also showed that group 1 was statistically different from the other two groups in all of the factors (P < 0.01).
Association between subtype and postoperative recurrence The postoperative recurrence rate was significantly different among three groups (Table 3). But there was no statistical difference between group 1 and group 2. Prognosis of patients with different subtypes 3-year survival rate of three groups were 96.4%, 61.0% and 40.5% respectively. There was a remarkable statistical difference among the three groups. And 3-year survival rate of group 1 was higher than the other two groups. The group 3 was the worst one (Fig. 5).
Discussion Pure BAC has been proposed in the recent 1999 and 2004 WHO classifications. In the WHO classification, BAC is now defined as adenocarcinoma without evidence of vascular, pleural, or stromal invasion [2, 3]. It’s been showed that pure BAC had an excellent prognosis (100% 5-year survival) [4] and 3-year survival rate in our research was 96.4%, higher than that of Ge et al [5]. According to the follow-up data in this group, only 1 70-year-old male patient died after operation for 29+ months, whose histological type was mucinous subtype. It has been suggested that age, pathological subtype, and tumor size may be important factors affecting their survival time. Whereas, if there is interstitial, vascular, or pleural invasion it should be diagnosed as adenocarcinoma, mixed subtype. The incidence of adenocarcinoma with BAC component is far higher than pure BAC. How to recognize and distinct them have been gradually attracted more attention of a number of researchers. With the development of molecular biology of cancer, EGFR-TKI has been successfully used in clinical therapy. Studies have been shown that AC with BAC component was sensitive to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. And it’s been reported that mutation of EGFR of pure BAC is lower than that of AC with BAC features. It can be speculated that pure BAC is different from AC with BAC component at the gene level, which brings different of treatment and prognosis. Some researchers think that it is a developmental progress from pure BAC to AC with BAC component, and then to AC without BAC component. And pure BAC is the early stage of adenocarcinoma [6]. Terasaki et al [7] had a retrospective analysis for patients of 441 cases, which were divided into three groups: BAC, AC consisting of BAC and invasive adenocarcinoma as well as invasive adenocarcinoma without BAC component. They thought that mixed-type adenocarcinoma consisiting of BAC was the moderate lesion between the other two types. We have observed that 3-year survival rate of BAC is the highest one among all the groups, which is consistent
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with related literature [8, 9]. Chen [10] et al thought that the part of AC with BAC features often appeared at the edge of tumors, which suggested the invasion of tumor weakly. A large number of studies have shown that patients with pure BAC or AC with most of BAC components have a better prognosis. Okada et al [11] thought that higher is the proportion of BAC components, weaker is the invasion of tumor. But other scholars thought adenocarcinoma with BAC components, even most of them was adenocarcinoma, its biological behavior was still close to BAC. We did not divide the group of AC with BAC component any more. But from the present observations, the recurrence rate of AC with BAC component is less than that of AC without BAC component after surgery, and the prognosis is better than the latter remarkablely. In addition, we also find AC with BAC features more often appears intrathoracic recurrence, but distant metastasis rarely. On the contrary distant metastasis in AC without BAC component is relatively more common, and mostly is brain metastasis. Another study suggests that occurrence of BAC is associated with environmental factors rather than smoking, and our data in this study also supports this point of view. Pure BAC and adenocarcinoma with BAC components often occur in the population of non-smoking and smoking rarely, which is suggested that these two types of AC could not have a strong relationship between cigarette exposure. In summary, we have shown that BAC component in mixed adenocarcinoma may still have the BAC feature in the sub-cellular structure, but its invasion becomes strong and prognosis gets worse. Thus the prognosis among the three groups has a significant difference (P < 0.01). In our research, it suggests that pure BAC, AC with BAC component and AC without BAC component have completely different clinical and pathological characteristics and prognosis, which will have a substantial significance for instituting clinical treatment strategies
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scientifically and rationally and assessing the prognosis of patients with adenocarcinoma. They should be strictly distinguish in clinic.
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