Study on the relationship between PTHrP gene expression and differentiation of oral squamous cell carcinoma

我们发现甲状旁腺激素相关蛋白（PTHrP）、氨基酸1-34的免疫染色与口腔鳞状细胞癌（OSCC）角化和恶性的组织学分级相关。口腔颌面协会。外科医生。1997，京都)。目的是确定PTHrP mRNA的表达是否与PTHrP 1-34的免疫组化染色和角化有关。本研究使用了33例患者的活检标本，其中11例女性，22例男性，OSCC和4例正常粘膜标本。采用先前描述的免疫组织化学染色方法（LSAB法），用多克隆1-34抗体和非同位素原位杂交对5 μm厚度的石蜡切片进行染色。我们使用地高辛标记的寡核苷酸探针，该探针与编码PTHrP 6-16氨基酸序列的人PTHrP mRNA互补。切片用Mayer氏苏木精反染。30/33例（91%）标本中存在PTHrP mRNA阳性信号。通过免疫组化检查将所有标本分为两组，一组为轻微染色，另一组为强烈染色。虽然强染色组mRNA阳性信号百分比（100%,13/13）高于弱染色组（85%,17/20），但通过mRNA表达难以区分两组。提示PTHrP的转录对口腔癌的角化或分化影响不大。PTHrP的翻译后加工可能是造成这一现象的主要原因。需要进一步的研究来阐明这个问题。日本文部科学省资助（No.10470443）部分资助。

We found that immunostain of parathyroid hormone related protein, PTHrP, amino acids 1-34 correlated with a histological grading for keratinization and malignancy of oral squamous cell carcinoma, OSCC (abstract, the Int.Association of Oral ＆ Maxillofac. Surgeons. 1997, Kyoto). The purpose was to determine whether the expressin of the mRNA of PTHrP is related to the immunohistochemical stains of PTHrP 1-34 and keratinization. Biopsy specimens from 33 patients, 11 females and 22 males, with OSCC and 4 normal mucosal specimens were used of this study. A previously described method of immunohistochemical staining (LSAB method) with polyclonal 1-34 antibodies and non-isotopic in situ hybridization were performed on 5 μm thickness paraffin sections. We used digoxigenin labeled oligonucleotide probe which was complement to the human PTHrP mRNA coding for the amino acid sequence PTHrP 6-16. The sections were counterstained with Mayer's hematoxylin. Positive signals of PTHrP mRNA were present in 30/33 (91%) specimens. All specimens were classified in two groups, one showed slight stains and another showed intense staining by the immunohistochemical investigation. Although the percentage(100%, 13/13) of positive signals of the mRNA in the intense stain group is higher than that(85%, 17/20) in the weak stain group, it was difficult to distinguish two groups by expression of mRNA.The results suggest that transcription of PTHrP might not affect much to keratinication or differentiation of oral cancer. Post translational processing of PTHrP may take a major role for this phenomenon. Additional study is required to elucidate this issue. Partially supported by a Grant-in-aid (No.10470443) from the Ministry of Education Science, and Culture of Japan.