Nogueira E, Navarro S, Pellín A, Llombart-Bosch A
Department of Pathology, University of Valencia Medical School, Spain.
Diagn Mol Pathol. 1997 Feb;6(1):10-6. doi: 10.1097/00019606-199702000-00003.
Trk receptors have been identified by immunohistochemical methods in primitive neuroectodermal tumor (PNET)/Ewing's sarcoma (ES). However, the presence of different members of the Trk family of receptors in PNET/ES has not been specified. We have examined whether Trk A, B, and C receptors are specifically expressed in ES both with and without features of neural differentiation. Ten ES tumors (five primary tumors of bone and five extraosseous tumors transplanted into nude mice) were investigated for expression of Trk receptors by immunohistochemistry and reverse transcription-polymerase chain reaction. One primary ES and the five grafted ES tumors exhibited signs of neural differentiation; the remaining four primaries were undifferentiated ES. Other tumor types were analyzed as controls; they included three neuroblastomas (NB), two lymphomas, and single cases of pheochromocytoma (PHEO), schwannoma (SCHW), osteosarcoma, and carcinoma of breast, colon, and kidney. Trk receptors were detected in paraffin-embedded tumor tissue sections by means of a pan-Trk polyclonal antibody raised against the 14 carboxy-terminal residues of gp140trk, and trk A, B, and C transcripts were specifically detected by polymerase chain reaction-based amplification on cDNAs derived from tumor RNA with MuLV reverse transcriptase. Reactivity to the pan-Trk antibody was exhibited by six ES tumors, the three NBs, and the single PHEO and SCHW cases; immunoreactivity was restricted to differentiated tumors, in the case of ES. Tumor types positive for immunostaining were also distinguished by containing transcripts of TRK genes. However, the trk A, B, and C expression pattern of ES differed from that of NBs, PHEO, and SCHW. Transcripts of trk A, B, and C were detected in seven, four, and one case of ES, respectively, and in five, two, and five cases of NB, PHEO, and SCHW, respectively. Interestingly, all differentiated ES tumors contained trk A transcripts. Tumors of neuroectodermal phenotype and/or derivation were thus characterized by a distinct consensus expression pattern: trk A+/B-/C+ for differentiated ES and trk A+/B-/C+ for NB-PHEO-SCHW. These results indicate that the TRK gene family is frequently activated in ES; they also suggest that Trk A receptor is a feature of ES with neural differentiation, whereas Trk B and C receptors seem to be present in undifferentiated ES.
通过免疫组织化学方法已在原始神经外胚层肿瘤（PNET）/尤因肉瘤（ES）中鉴定出Trk受体。然而，PNET/ES中Trk受体家族不同成员的存在情况尚未明确。我们研究了Trk A、B和C受体在具有和不具有神经分化特征的ES中是否特异性表达。通过免疫组织化学和逆转录-聚合酶链反应对10例ES肿瘤（5例原发性骨肿瘤和5例移植到裸鼠体内的骨外肿瘤）进行Trk受体表达情况的研究。1例原发性ES和5例移植的ES肿瘤表现出神经分化迹象；其余4例原发性肿瘤为未分化ES。分析其他肿瘤类型作为对照，包括3例神经母细胞瘤（NB）、2例淋巴瘤以及嗜铬细胞瘤（PHEO）、神经鞘瘤（SCHW）、骨肉瘤、乳腺癌、结肠癌和肾癌各1例。通过针对gp140trk的14个羧基末端残基产生的泛Trk多克隆抗体在石蜡包埋的肿瘤组织切片中检测Trk受体，并用基于聚合酶链反应的方法在由肿瘤RNA经莫洛尼鼠白血病病毒逆转录酶逆转录得到的cDNA上特异性检测trk A、B和C转录本。6例ES肿瘤、3例NB以及1例PHEO和1例SCHW病例对泛Trk抗体有反应；就ES而言，免疫反应仅限于分化肿瘤。免疫染色阳性的肿瘤类型也通过含有TRK基因转录本得以区分。然而ES中trk A、B和C的表达模式与NB、PHEO和SCHW不同。trk A、B和C转录本分别在7例、4例和1例ES中检测到，在5例、2例和5例NB、PHEO和SCHW中检测到。有趣的是，所有分化的ES肿瘤都含有trk A转录本。因此，具有神经外胚层表型和/或起源的肿瘤具有独特的共同表达模式：分化的ES为trk A+/B-/C+，NB-PHEO-SCHW为trk A+/B-/C+。这些结果表明TRK基因家族在ES中经常被激活；它们还表明Trk A受体是具有神经分化的ES的一个特征，而Trk B和C受体似乎存在于未分化的ES中。
