A. Biology: It
is an oncogene product from
the bcl-2 locus at
18(q21). It is accentuated
in lymphomas that have the t (14;18) (q32;q21) translocation,
which apposes bcl-2
with immunoglobulin heavy chain. The
product inhibits apoptosis. It
is present in mitochondria. It
acts by inhibiting cytochrome-c, which is the first step in caspase-9
release. Caspase-9
causes apoptosis.
B. Normal
distribution: Mantle
zone in lymph nodes, memory B-cells, inter-follicular T-cells,
and thymic cortex. Normal
and reactive germinal centers are negative, but there may be
an occasional positive intra-follicular T-cell. Cellular
distribution is cytoplasmic (mitochondria) and membrane.
C. Use: Distinguish
reactive follicular hyperplasia from follicular lymphoma.
1. Low
grade (predominantly small cleaved: 97%
of cases positive
2. Intermediate
grade (mixed cell type): 83% " " positive
3. High
grade (predominantly large): 74% " " "
D. Other
Diseases:
1. Medullary
carcinoma of thyroid: 79%
positive. Better
prognosis if positive.
2. GIST: Similar
to CD 34. Not helpful.
3. Adrenal
adenomas and carcinomas positive. Not
helpful.
4. Urinary
bladder: variable
positivity. Not
helpful.
5. May
be positive in Hairy Cell Leukemia and some cases of CLL. Neither
of these have the t(14;18).
6. Diffuse
Large Cell Lymphoma: 25%
may be positive.
7. Bcl-2 positive breast cancers have better prognosis in any given NPI ctaegory.
E. Fixative: IHC
works with NBF or mercury based. If
there is a choice, formalin is preferred.
General
references:
1. Neoplastic
Hematopathology, Lippincott Williams & Wilkins, 2nd ed,
2001. Knowles, Daniel
M., ed.
2. Diagnostic
Immunohistochemistry, Churchill Livingstone, 2002. Dabbs,
David J. ed.
3. Callagy GM, Ellis IO, et. al., "Bcl-2 Is a Prognostic Marker in Breast Cancer Independently of the Nottingham Prognostic Index", 2006 [here].
(posted
4 June 2002; latest update 21 March 2010) |
