PMID- 10433944
OWN - NLM
STAT- MEDLINE
DCOM- 19990831
LR  - 20181113
IS  - 0002-9440 (Print)
IS  - 0002-9440 (Linking)
VI  - 155
IP  - 2
DP  - 1999 Aug
TI  - Hereditary and sporadic papillary renal carcinomas with c-met mutations share a
      distinct morphological phenotype.
PG  - 517-26
AB  - Germline mutations of c-met oncogene at 7q31 have been detected in patients with 
      hereditary papillary renal cell carcinoma. In addition, c-met mutations were
      shown to play a role in 13% of patients with papillary renal cell carcinoma and
      no family history of renal tumors. The histopathology of papillary renal cell
      carcinoma with c-met mutations has not been previously described. We analyzed the
      histopathology of 103 bilateral archival papillary renal cell carcinomas and 4
      metastases in 29 patients from 6 hereditary papillary renal cell carcinoma
      families with germline c-met mutations and 6 papillary renal cell carcinomas with
      c-met mutations from 5 patients with no family history of renal tumors.
      Twenty-five sporadic renal tumors with prominent papillary architecture and
      without somatic c-met mutations were evaluated for comparison. All papillary
      renal cell carcinomas with c-met mutations were 75 to 100%
      papillary/tubulopapillary in architecture and showed chromophil basophilic,
      papillary renal cell carcinoma type 1 histology. Fuhrman nuclear grade 1-2 was
      seen in tumors from 23 patients, and nuclear grade 3 was observed focally in 8
      patients. Seventeen patients had multiple papillary adenomas and microscopic
      papillary lesions in the surrounding renal parenchyma. Clear cells with
      intracytoplasmic lipid and glycogen were focally present in tumors of 94%
      papillary renal cell carcinoma patients. Clear cells of papillary renal cell
      carcinoma had small basophilic nuclei, and clear cell areas lacked a fine
      vascular network characteristic of conventional (clear) cell renal cell
      carcinoma. We conclude that papillary renal cell carcinoma patients with c-met
      mutations develop multiple, bilateral, papillary macroscopic and microscopic
      renal lesions. Renal tumors with c-met genotype show a distinctive papillary
      renal cell carcinoma type 1 phenotype and are genetically and histologically
      different from renal tumors seen in other hereditary renal syndromes and most
      sporadic renal tumors with papillary architecture. Although all hereditary and
      sporadic papillary renal cell carcinomas with c-met mutations share papillary
      renal cell carcinoma type 1 histology, not all type 1 sporadic papillary renal
      cell carcinomas harbor c-met mutations.
FAU - Lubensky, I A
AU  - Lubensky IA
AD  - Laboratory of Pathology, National Cancer Institute, Bethesda, Maryland, USA.
      lubensky@box-l.nih.gov
FAU - Schmidt, L
AU  - Schmidt L
FAU - Zhuang, Z
AU  - Zhuang Z
FAU - Weirich, G
AU  - Weirich G
FAU - Pack, S
AU  - Pack S
FAU - Zambrano, N
AU  - Zambrano N
FAU - Walther, M M
AU  - Walther MM
FAU - Choyke, P
AU  - Choyke P
FAU - Linehan, W M
AU  - Linehan WM
FAU - Zbar, B
AU  - Zbar B
LA  - eng
GR  - N01-CO-56000/CO/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
SB  - IM
MH  - Adenoma/genetics/pathology
MH  - Adult
MH  - Aged
MH  - Carcinoma, Papillary/*genetics/*pathology
MH  - Chromosomes, Human, Pair 7
MH  - Family Health
MH  - Female
MH  - *Germ-Line Mutation
MH  - Humans
MH  - Kidney Neoplasms/*genetics/*pathology
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Metastasis
MH  - Pedigree
MH  - Phenotype
MH  - Proto-Oncogene Proteins c-met/*genetics/metabolism
MH  - Trisomy
PMC - PMC1866853
EDAT- 1999/08/06 00:00
MHDA- 1999/08/06 00:01
CRDT- 1999/08/06 00:00
PHST- 1999/08/06 00:00 [pubmed]
PHST- 1999/08/06 00:01 [medline]
PHST- 1999/08/06 00:00 [entrez]
AID - S0002-9440(10)65147-4 [pii]
AID - 10.1016/S0002-9440(10)65147-4 [doi]
PST - ppublish
SO  - Am J Pathol. 1999 Aug;155(2):517-26. doi: 10.1016/S0002-9440(10)65147-4.