Journal List > Tuberc Respir Dis > v.70(2) > 1001584

Yoon, Kim, Shin, Kim, Cho, Kim, Park, Jeon, Kim, Lee, Lee, and Park: Maspin Expression and Its Clinical Significance in Non-Small Cell Lung Cancer

Abstract

Background

Maspin (mammary serine protease inhibitor) is a member of the serpin superfamily. A few studies have examined the role of maspin in tumor suppression of non-small cell lung cancer (NSCLC); however, its role in the development and progression of NSCLC still remains controversial. We evaluated the immunohistochemical expression of maspin in order to elucidate its clinical significance in NSCLC.

Methods

We analyzed 145 patients with pathologically confirmed NSCLC, including 66 cases of squamous cell carcinomas (SCCs) and 79 cases of adenocarcinomas (ADCs). We performed a immuno-histochemical stain with maspin and PCNA (proliferating cell nuclear antigen) using tissue microarray blocks.

Results

There were 108 men and 37 women in the study population. The mean age of patients in the study was 63.7 years (range, 40.0~82.0; median, 65.0). The proportion of maspin expression was significantly higher in SCCs (52/66, 78.8%; p<0.01) than in ADCs (17/79, 21.5%; p<0.01). Maspin expression was not associated with PCNA (p=0.828), lymph node involvement (p=0.483), or tumor stage (p=0.216), but showed correlation with well-to-moderate tumor differentiation (p=0.012). There was no observed correlation between maspin expression and survival with NSCLC (p=0.218).

Conclusion

The present study suggests that maspin expression was significantly higher in SCCs than in ADCs and was associated with low histological grade. However, maspin expression was not an independent factor to predict a prognosis in NSCLC.

Figures and Tables

Figure 1
Immunohistochemical staining for maspin using the tissue microarray (×200). (A) ADC without maspin expression. (B) ADC with maspin expression. (C) SCC without maspin expression. (D) SCC with maspin expression.
trd-70-132-g001
Figure 2
Comparison of cumulative survival according to maspin expression in non-small cell lung cancer.
trd-70-132-g002
Table 1
Data sheet for maspin and PCNA
trd-70-132-i001

Gpab: polyclonal gout antibody; PCNA: proliferating cell nuclear antigen; Mmab: monoclonal mouse antibody.

Table 2
Characteristics of patients and maspin expression
trd-70-132-i002

Values are presented as number (%) unless otherwise indicated.

Table 3
Relationship between maspin expression and clinicopathologic features
trd-70-132-i003

Values are presented as number (%).

*Regardless of histologic type, maspin expression was significantly associated with low histological grade (p-value: SCC, <0.01; ADC, 0.04); I, II vs. IIIA ↑.

Table 4
Relationship between maspin expression and PCNA
trd-70-132-i004

NSCLC: non-small cell lung cancer; SCC: squamous cell carcinoma; ADC: adenocarcinoma; PCNA: pro-liferating cell nuclear antigen.

Table 5
Multivariate analysis of the prognostic factors in non-small cell lung cancer
trd-70-132-i005

PCNA: proliferating cell nuclear antigen; CI: confidence interval.

Notes

This work was supported for two years by Pusan National University Research Grant.

References

1. Zou Z, Anisowicz A, Hendrix MJ, Thor A, Neveu M, Sheng S, et al. Maspin, a serpin with tumor-suppressing activity in human mammary epithelial cells. Science. 1994. 263:526–529.
2. Pemberton PA, Tipton AR, Pavloff N, Smith J, Erickson JR, Mouchabeck ZM, et al. Maspin is an intracellular serpin that partitions into secretory vesicles and is present at the cell surface. J Histochem Cytochem. 1997. 45:1697–1706.
3. Sheng S, Carey J, Seftor EA, Dias L, Hendrix MJ, Sager R. Maspin acts at the cell membrane to inhibit invasion and motility of mammary and prostatic cancer cells. Proc Natl Acad Sci USA. 1996. 93:11669–11674.
4. Sheng S, Truong B, Fredrickson D, Wu R, Pardee AB, Sager R. Tissue-type plasminogen activator is a target of the tumor suppressor gene maspin. Proc Natl Acad Sci USA. 1998. 95:499–504.
5. Umekita Y, Ohi Y, Sagara Y, Yoshida H. Expression of maspin predicts poor prognosis in breast-cancer patients. Int J Cancer. 2002. 100:452–455.
6. Bièche I, Girault I, Sabourin JC, Tozlu S, Driouch K, Vidaud M, et al. Prognostic value of maspin mRNA expression in ER alpha-positive postmenopausal breast carcinomas. Br J Cancer. 2003. 88:863–870.
7. Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer statistics, 2007. CA Cancer J Clin. 2007. 57:43–66.
8. Korea National Statistical Office. Deaths and death rate by cause. 2007. Daejeon: Korea National Statistical Office.
9. Buccheri G, Ferrigno D. Prognostic value of stage grouping and TNM descriptors in lung cancer. Chest. 2000. 117:1247–1255.
10. Smith SL, Watson SG, Ratschiller D, Gugger M, Betticher DC, Heighway J. Maspin - the most commonly-expressed gene of the 18q21.3 serpin cluster in lung cancer - is strongly expressed in preneoplastic bronchial lesions. Oncogene. 2003. 22:8677–8687.
11. Hirai K, Koizumi K, Haraguchi S, Hirata T, Mikami I, Fukushima M, et al. Prognostic significance of the tumor suppressor gene maspin in non-small cell lung cancer. Ann Thorac Surg. 2005. 79:248–253.
12. Mountain CF. Revisions in the international system for staging lung cancer. Chest. 1997. 111:1710–1717.
13. Ngamkitidechakul C, Warejcka DJ, Burke JM, O'Brien WJ, Twining SS. Sufficiency of the reactive site loop of maspin for induction of cell-matrix adhesion and inhibition of cell invasion. Conversion of ovalbumin to a maspin-like molecule. J Biol Chem. 2003. 278:31796–31806.
14. Futscher BW, Oshiro MM, Wozniak RJ, Holtan N, Hanigan CL, Duan H, et al. Role for DNA methylation in the control of cell type specific maspin expression. Nat Genet. 2002. 31:175–179.
15. Yatabe Y, Mitsudomi T, Takahashi T. Maspin expression in normal lung and non-small-cell lung cancers: cellular property-associated expression under the control of promoter DNA methylation. Oncogene. 2004. 23:4041–4049.
16. Hendrix MJ. De-mystifying the mechanism(s) of maspin. Nat Med. 2000. 6:374–376.
17. Zou Z, Gao C, Nagaich AK, Connell T, Saito S, Moul JW, et al. p53 regulates the expression of the tumor suppressor gene maspin. J Biol Chem. 2000. 275:6051–6054.
18. Maass N, Hojo T, Ueding M, Lüttges J, Klöppel G, Jonat W, et al. Expression of the tumor suppressor gene Maspin in human pancreatic cancers. Clin Cancer Res. 2001. 7:812–817.
19. Maass N, Teffner M, Rösel F, Pawaresch R, Jonat W, Nagasaki K, et al. Decline in the expression of the serine proteinase inhibitor maspin is associated with tumour progression in ductal carcinomas of the breast. J Pathol. 2001. 195:321–326.
20. Nakagawa M, Katakura H, Adachi M, Takenaka K, Yanagihara K, Otake Y, et al. Maspin expression and its clinical significance in non-small cell lung cancer. Ann Surg Oncol. 2006. 13:1517–1523.
21. Kim S, Han J, Kim J, Park C. Maspin expression is transactivated by p63 and is critical for the modulation of lung cancer progression. Cancer Res. 2004. 64:6900–6905.
22. Katakura H, Takenaka K, Nakagawa M, Sonobe M, Adachi M, Ito S, et al. Maspin gene expression is a significant prognostic factor in resected non-small cell lung cancer (NSCLC). Maspin in NSCLC. Lung Cancer. 2006. 51:323–328.
TOOLS
Similar articles