LWBK1006-21 LWW-Govindan-Review December 12, 2011 19:6
Chapter 21•Genitourinary Cancer 289Answer 21.4. The answer is A.
Several prognostic factors have been identified that can help explain the
highly heterogeneous natural history of metastatic renal cancer. Hyper-
calcemia, poor performance status, and anemia are significant prognostic
factors in most studies. Age, in and of itself, is not a prognostic factor.Answer 21.5. The answer is A.
Of the choices, phase III data supportive of a survival benefit in a patient
with poor prognosis such as this are available only for temsirolimus. The
available data suggest that sunitinib or sorafenib could be considered.
However, data suggest that interferon is not effective in patients with poor
prognosis, and phase III data show that sunitinib is more effective than
interferon for metastatic disease in patients with a good and intermediate
prognosis.Answer 21.6. The answer is A.
Von Hippel-Lindau disease, caused by mutation of the VHL gene, is an
autosomal-dominant cancer syndrome characterized by multiple renal
cysts, early onset and multiple renal tumors, retinal angiomas and central
nervous system hemangioblastomas, pheochromocytomas, and pancre-
atic islet cell tumors. The Birt-Hogg-Dube syndrome, caused by muta-
tions of the BHD gene, is characterized by early onset chromophobe
cancers, benign hair follicle tumors (fibrofolliculomas), and pulmonary
cysts. Hereditary papillary renal cancer, caused by mutations of the MET
gene, is characterized by multiple type I papillary cancers. The heredi-
tary leiomyomatosis and renal cancer syndrome, caused by mutation of
the fumarate hydratase gene, is characterized by cutaneous and uterine
leiomyomas and aggressive type II papillary cancers.Answer 21.7. The answer is D.
VHL is part of the normal oxygen sensing and response system in all
cells and is mutated or altered in greater than 60% of sporadic clear cell
carcinomas of the kidney. Under normoxic conditions, VHL is part of a
multiprotein complex that recognizes the hydroxylated HIF transcription
factor, acts as a ubiquitin ligase, and thus targets it for proteasomal degra-
dation. Under hypoxic conditions, HIF is not hydroxylated, not targeted
to VHL and thus not degraded leading to upregulation of multiple genes
critical for the hypoxic response including vascular endothelial growth
factor. The VHL gene is expressed constitutively.Answer 21.8. The answer is D.
The tumor suppressor genes TP53, RB1 CDKN2A, and PTEN are impli-
cated in the pathogenesis of invasive bladder cancer.Answer 21.9. The answer is A.
Indications for intravesical therapy are multiple recurrent Ta lesions, espe-
cially if they are high grade, or T cis. It is critical that the pathologic