Attard G, Jameson C, Moreira J, Flohr P, Parker C, Dearnaley D, Cooper C S, de Bono J S
The Royal Marsden NHS Foundation Trust, Sutton, UK.
J Clin Pathol. 2009 Apr;62(4):373-6. doi: 10.1136/jcp.2008.061515. Epub 2008 Dec 9.
Fusion of the hormone-regulated gene TMPRSS2 with ERG occurs in 50-70% of prostate cancers; fusions of ETV1 with one of several partners occur in approximately 10% of prostate cancers. These two translocations are mutually exclusive. The presence of subclasses of these chromosomal rearrangements may indicate worse prognosis, with the subclass 2+Edel, which has duplication of TMPRSS2:ERG fusion sequences, indicating particularly poor survival. However as this case shows, significant heterogeneity can exist with ERG and ETV1 rearrangements occurring in both prostate intra-epithelial neoplasia and cancer in the same prostatectomy specimen and with adjacent cancer areas containing a single copy, duplication and even triplication of the rearranged locus. As the majority of ETS gene fusions are hormone regulated, they could explain the pathogenesis underlying exquisitely hormone-sensitive prostate cancer. This is exemplified by the case presented here of a patient diagnosed in 1991 who remains asymptomatic and chemotherapy-naïve after having long-lasting tumour responses to multiple lines of systemic hormonal treatments.
激素调节基因TMPRSS2与ERG的融合出现在50%-70%的前列腺癌中；ETV1与多个伙伴之一的融合出现在约10%的前列腺癌中。这两种易位相互排斥。这些染色体重排亚类的存在可能预示着更差的预后，其中2+Edel亚类具有TMPRSS2:ERG融合序列的重复，提示生存尤其不佳。然而，正如本病例所示，同一前列腺切除标本中的前列腺上皮内瘤变和癌中均可出现ERG和ETV1重排，且相邻癌区的重排位点存在单拷贝、重复甚至三倍体，存在显著的异质性。由于大多数ETS基因融合受激素调节，它们可以解释激素高度敏感型前列腺癌的发病机制。1991年诊断的一名患者的病例即为例证，该患者在对多线全身激素治疗产生持久肿瘤反应后仍无症状且未接受过化疗。
