LWBK1006-03 LWW-Govindan-Review November 24, 2011 11:19
Chapter 3•Etiology of Cancer Part 1 49gene promoters. IL-2 and IL-2 receptor are the most relevant genes acti-
vated by Tax. Adult T cells constitutively express the alpha chain of IL-2
receptor at high levels, and this can stimulate proliferation of infected
cells. The site of integration of the viral genome is random and differ-
ent from patient to patient, indicating that insertional mutagenesis does
not play a role in the transforming effect of HTLV1. The long latency
period between the onset of the infection and the development of the
malignancy suggests that HTLV1 genome does not contain an acutely
transforming oncogene. Unlike HIV, HTLV1 does not have an immuno-
suppressive effect.Answer 3.24. The answer is B.
HTLV2 shares 70% homology at the amino acid level with HTLV1. The
virus was isolated from a patient with atypical T-cell variant hairy cell
leukemia, but convincing epidemiologic data for an etiologic role for
HTLV2 in any human disease do not exist. HTLV2 is also transmitted
by the same routes as HTLV1 and is found in 0.01% of blood donors and
in a larger proportion of intravenous drug users.Answer 3.25. The answer is C.
HIV, unlike HTLV1, the other retrovirus with transforming effects in
humans, does not have a direct oncogenic effect. None of the HIV pro-
teins have a directly transforming effect, and none of the proteins are
known to enhance the expression of any of the cellular oncogenes. Rarely,
insertional mutagenesis resulting in T-cell lymphomas has been reported
in HIV-infected patients. However, this disease does not occur dispro-
portionately in HIV-infected patients, making the observation of inser-
tional mutagenesis in some patients with T-cell lymphomas as a random
event rather than a specific oncogenic transforming effect of the virus.
Many of the malignancies observed in HIV-infected patients, including
the AIDS-defining cancers such as cervical cancer or non-Hodgkin’s lym-
phoma, are associated with coinfection by DNA viruses. Infection with
these viruses and the subsequent transforming effect are facilitated by the
state of immune suppression induced by the HIV infection.Answer 3.26. The answer is D.
KS tumors are histologically complex tumors. The predominant cell and
the most likely candidate tumor cell of KS is the spindle cell, but the tumor
also consists of inflammatory cells and angiogenic cells. A polyclonal, mul-
ticentric proliferative process seems to occur, which is reflected in the fre-
quently observed waxing and waning clinical course of KS. HHV-8 is the
primary etiologic agent of KS in HIV-infected and noninfected patients.
The role of HIV in the pathogenesis of KS is related to its ability to sup-
press immunity. In addition to the immune suppression, secretion of Tat
protein by HIV-infected cells contributes to the production of cytokines,
such as vascular endothelial growth factor, and these factors enhance the
proliferation of the endothelial cells. HIV does not have any direct trans-
forming effect on endothelial cells.