Correlation of HB-EGF Paracrine and Autocrine with Advanced Stages of Malignant Mixed Mullerian Tumor.
Lei Zhang, David Shimizu, Stacey A Honda, Jeffrey Killeen, Ian Pagano, Michele Carbone. University of Hawaii, Honolulu
Background: HB-EGF(Heparin binding-epidermal growth factor like growth factor)is a secretary protein released by either target cells(autocrine) or cells nearby(paracrine) to promote epithelial-mesenchymal transition, tumor growth, invasion and metastasis. Malignant Mixed Mullerian tumor(MMMT) is a carcinoma with malignant mesenchymal transition. The aim of this study is to estimate HB-EGF secretion pattern in MMMT and how it is correlated to tumor staging.
Design: 44 cases of MMMT were selected including stage I (13), II(3), III(18), and IV(10). RNA was extracted from formalin fixed paraffin embedded blocks representing primary tumor and adjacent normal through macrodissection. HB-EGF expression was detected through RT-PCR and normalized by GAPDH(Glyceraldehyde 3-phosphate dehydrogenase).
Results: 1). Paracrine was defined as normalized HB-EGF ratio between normal and tumor higher than 25, e.g. N:T > 25. Although the absolute HB-EGF amount of adjacent normal was not defined in paracrine classification, the HB-EGF of normal tissue in paracrine (N:paracrine) showed an overall increase comparing with tumor(T) and normal(N) in non-autocrine, non-paracrine cases[Figure 1].
2). Autocrine was defined as normalized HB-EGF level more than 0.5 in tumor. This cutoff is higher than any 95% confidence interval of N, T and N:paracrine in [Figure 1].
3). By aforementioned criteria, the MMMT stage III/IV showed an increased percentile of combined autocrine and paracrine(39.3%) compared with MMMT stage I/II (12.5%), p=0.05. [Table 1]
|Tumor stages||Case No||Paracrine||Autocrine||Percentile of combined paracrine and autocrine|
|I & II||16||2||0||(2+0)/16 = 12.5%|
|III & IV||28||8||3||(8+3)/28 = 39.3%|