Expression of CD34, alpha-smooth muscle actin, and transforming growth factor beta1 in squamous intraepithelial lesions and squamous cell carcinoma of the larynx and hypopharynx.
OBJECTIVE
There is increasing evidence that stromal reaction in cancer has an important diagnostic and prognostic significance. Recent studies have shown that CD34-positive stromal cells and myofibroblasts may play an important role in host response to invasive cancer. The aim of our study was to analyze the expression of CD34, alpha-smooth muscle actin (SMA), and transforming growth factor beta1 (TGFbeta1) in squamous intraepithelial lesions (SILs) and squamous cell carcinoma (SCC) of the larynx and hypopharynx, to establish their significance, and to elucidate the mechanism of myofibroblast formation.


METHODS
Immunohistochemistry was performed on samples of 42 resected larynges and 12 laryngeal biopsies of SILs and SCC using antibodies against SMA, CD34, CD31, TGFbeta1, and TGFbeta1 receptors. The expression of TGFbeta1 mRNA was detected with RNA in situ hybridization using specific oligonucleotides for TGFbeta1.


RESULTS
The stroma in normal laryngeal mucosa and SILs contained scattered CD34-positive cells, but there were no SMA-positive myofibroblasts. In contrast, the stroma of SCC contained SMA-positive myofibroblasts, but there were no CD34-positive stromal cells. This pattern of stromal reaction was also observed in the peritumoral zone. In adjacent normal tissue, there were CD34-positive stromal cells and no myofibroblasts. We found more intense TGFbeta1 expression in carcinoma cells than in the normal laryngeal epithelium and positive staining for both TGFbeta1 receptors on stromal cells of the normal mucosa. In SCC, many myofibroblasts expressed TGFbeta1 and both receptors for TGFbeta1. Expression of TGFbeta1 mRNA was similar to expression of TGFbeta1 protein.


CONCLUSIONS
Our study shows that disappearance of CD34-positive stromal cells and appearance of SMA-positive stromal myofibroblasts are associated with transformation of laryngeal SILs to SCC. This pattern of stromal reaction was found not only in the tumor but also in the peritumoral zone, defined as a band of host tissue between the invasive tumor front and adjacent normal tissue. Our findings also support the suggestion that overproduced TGFbeta1 in carcinoma cells mediates one of the mechanisms of transformation of stromal cells to myofibroblasts in laryngeal carcinogenesis.
Kojc
Nika
N
Medical Faculty, Institute of Pathology, University of Ljubljana, Slovenia. nika.kojc@mf.uni-lj.si
Zidar
Nina
N
Vodopivec
Boris
B
Gale
Nina
N
D000199:Actins / Q000096:biosynthesis; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000096:biosynthesis; D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D005260:Female; D006801:Humans; D007013:Hypopharynx / Q000473:pathology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007822:Laryngeal Neoplasms / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009130:Muscle, Smooth / Q000378:metabolism; D011230:Precancerous Conditions / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D053773:Transforming Growth Factor beta1
D000199:Actins; D018952:Antigens, CD34; D014408:Biomarkers, Tumor; D012333:RNA, Messenger; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1