Page 160 - Concise Pathology for Exam Preparation ( PDFDrive )

6 Neoplasia 145

(c) Hepatitis viruses: 70–80% hepatocellular carcinoma is due to HBV and HCV. Ef-
fects of HBV are mainly indirect; it causes chronic liver cell injury, and regenerative
hyperplasia (increased pool of cycling cells are at risk for genetic changes). HBV
also encodes a regulatory element called HBX protein, which disrupts normal
growth control of infected liver cells by transcriptional activation of an insulin-like
growth factor II and receptors for insulin-like growth factor I. It also binds to P53
and interferes with its growth-suppressing activities.
(d) Human herpes simplex virus (HHV) 8: HHV 8 has an established role in Kaposi
sarcoma, B cell lymphomas and multicentric variant of Castleman disease. HHV-8
infects host macrophages and primitive mesenchymal cells, which differentiate into
endothelial cells under the influence of several cytokines like IL6, IL8 and MIP.
2. Oncogenic RNA viruses:
• Retroviruses are the only RNA viruses that seem to have oncogenic potential in hu-
mans. They contain ‘reverse transcriptase’, which induces reverse transcription of viral
RNA to synthesize viral DNA. The viral DNA moves to host cell nucleus and gets in-
corporated in it. The prototypic example of an oncogenic RNA virus is human T cell
leukemia virus (HTLV)-1.
• HTLV-1 causes adult T cell leukaemia–lymphoma (ATLL) endemic in Japan and
Caribbean basin.
• It has tropism for CD41 T cells and is transmitted by passage of infected T cells
during sexual intercourse, blood product transfusion and breast feeding.
• It contains gag, pol and env genes typical of other retroviruses. It also contains ‘TAX’
gene, which activates several host cell genes involved in proliferation and differen-
tiation of T cells and interferes with DNA repair functions.
3. Helicobacter pylori: Can be demonstrated in 90% cases of gastritis and 20–30% cases
of gastric ulcer, and is also implicated in the pathogenesis of gastric carcinoma and
lymphoma (Flowchart 6.9). It induces active B cell proliferation, which predisposes to
acquisition of genetic abnormalities, eg, translocation (11; 18).
Differences between DNA and RNA oncogenic viruses are summarized in Table 6.8.

H. pylori
Chronic gastritis

Multifocal atrophy and decreased gastric acid secretion
Intestinal metaplasia

Dysplasia

Carcinoma (adenocarcinoma of intestinal type)
FLOWCHART 6.9. Mechanism of Helicobacter pylori-induced oncogenesis.

TABLE 6.8. Differences between DNA and RNA oncogenic viruses
Features DNA oncogenic virus RNA oncogenic virus
Viruses HPV, EBV, HBV, KSHV HTLV-1
Genome Double-stranded DNA Single-stranded RNA
Reverse transcriptase Absent Present
Interaction with Linear DNA genome forms a double-stranded cir- First RNA is transcribed into
host genome cle within infected cell and then covalently DNA, which then integrates
integrates into the host genome into host genome
Name of gene Early region A gene src gene
Name of protein T antigen src protein
Function of protein Protein kinase, ATPase activity, binding to DNA and Protein kinase that phosphory-
stimulation of DNA lates tyrosine and disturbs the
growth control process
Location of protein Primarily nuclear, but sometimes in plasma membrane Plasma membrane

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