Annals of Oncology 15:843-844, 2004
© 2004 European Society for Medical Oncology
Papillary renal cell carcinoma and gastrointestinal stromal tumor: a unique association
Departments of 1 Medicine, 2 Surgery and 3 Pathology, University of Hong Kong, Queen Mary Hospital, Hong Kong, Republic of China
The repeated associations of specific tumors often serve as pointers to novel oncogene defects. We present three unusual cases of concurrent papillary renal cell carcinoma (PRCC) and gastrointestinal stromal tumor (GIST).
From 1999 to 2003, 86 cases of renal cell carcinoma (RCC) were diagnosed at Queen Mary Hospital, Hong Kong. The commonest histology was clear cell (n = 69; 80%), followed by papillary RCC (n = 11; 12.7%). Seven patients died from RCC, and a second tumor was found in 14 cases. These included breast cancer (n = 2), adenoma of colon and adrenals (n = 2 each), carcinoma of lung, bladder, esophagus and larynx (n = 1 each); and one case each of schwannoma, ovarian Brennar tumor and cerebellar hemangioblastoma (von Hippel Lindel syndrome patient). Interestingly, only three of 11 papillary RCC patients had second tumors, and all were GIST (P <0.001, Fisher’s exact test) (Table 1). As a cross-reference, second tumors were traced in the 74 new cases of GIST in the same period. A total of 23 GIST were diagnosed incidentally, either at resection of other tumors, including one case of PRCC (others: gut carcinoma, n = 11; liver tumor, n = 3; lymphoma, n = 1; fibroids, n = 3); or at laparotomy for other indications (n = 4). Among the other 51 symptomatic GIST cases, eight patients died of GIST and a second tumor was found in 12 cases, including two cases of PRCC. Other histology included benign adenoma (n = 5) and carcinoma of breast, prostate, esophagus, rectum and skin (n = 1 each).
|
From the 2000 Hong Kong Cancer Registry, GIST and RCC accounted for only 0.3% and 0.8% of all reported tumors. The exclusive PRCC histology and concurrent presentation in our cases hinted strongly at an etiological link. Reports from Sweden and New York also reported an increased incidence of second tumors in patients with PRCC, but not in those with other RCC histology [1, 2]. Primary gastrointestinal tumors were reported in 3.2% and 5.6% of cases, respectively, but the exact histological subtype was not recorded. It would be interesting to verify our novel association with a revisit of these large registries. Intriguingly, the only report of concurrent GIST and RCC in Caucasian patients also involved PRCC [3].
Both PRCC and GIST may occur as recurrent familial tumors, related to mutations in the proto-oncogenes c-MET and c-KIT. These are both receptor tyrosine kinase (RTK) molecules. Such germline mutations are rarely found in sporadic cases such as ours. Concurrent RTK related tumor of different histology is best described for multiple endocrine neoplasia syndrome 2A (medullary thyroid carcinoma, neuroma and pheochromocytoma) due to c-RET mutation [4]. Our current cases are novel in that concurrent RTK related tumors involved not only those of different histology, but implicated different RTK genes as well. One plausible speculative explanation is the presence of novel activating mutations in upstream regulatory pathways. The frequent co-expression of c-MET and c-KIT in solid tumors suggests the existence of common co-regulatory mechanisms [5]. Clinically, tyrosine kinase inhibitors (e.g. imatinib mesylate) that are effective against several RTK proto-oncogenes (e.g. c-KIT, abl) and tumors [chronic myeloid leukemia (CML), GIST] may represent a promising novel treatment approach for these patients.
REFERENCES
1. Czene K, Hemminki K. Familial papillary renal cell tumors and subsequent cancers: a nationwide epidemiological study from Sweden. J Urol 2003; 169: 1271–1275.[Medline]
2. Rabbani F, Reuter VE, Katz J, Russo P. Second primary malignancies associated with renal cell carcinoma: influence of histological type. Urology 2000; 56: 399–403.[CrossRef][Medline]
3. Voelzke BB, Sakamoto K, Hantel A et al. Gastrointestinal stromal tumor: involvement in urologic patients and recent therapeutic advances. Urology 2002; 60: 218–222.[Medline]
4. Schmidt L, Duh FM, Chen F et al. Germline and somatic mutations in the tyrosine kinase domain of the MET proto-oncogene in papillary renal carcinomas. Nat Genet 1997; 16: 68–73.[CrossRef][Web of Science][Medline]
5. Rygaard K, Nakamura T, Spang-Thomsen M. Expression of the proto-oncogenes c-met and c-kit and their ligands, hepatocyte growth factor/scatter factor and stem cell factor, in SCLC cell lines and xenografts. Br J Cancer 1993; 67: 37–46.[Web of Science][Medline]
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||