Richard A. Savage, MD
Q. We do MIB-1
staining on sections of invasive breast cancers to estimate the
size of the proliferative fraction. Excluding the use of image analysis
to help quantify the percentage of tumor cell nuclei staining, do
any reliable methodological guidelines exist beyond providing a
rough estimate, such as small, large, or intermediate-sized proliferative
A. I recommend doing careful mitotic figure counts and recording
the findings along with a carefully performed Bloom-Richardson grading
of the invasive breast component. I don't recommend Ki-67 labeling.
Previous studies have shown a close association between mitotic
figure counts and Ki-67 and bromodeoxyuridine-labeling indices in
Moreover, I do not know of a good standardized technique or method
for measuring and reporting Ki-67 labeling of breast carcinomas.
Indeed, a recently published large multicenter study (172 participating
laboratories) focused on the reproducibility of measuring Ki-67
labeling indices and found that excessive interlaboratory differences
were the consequence of poor technique standardization.3
If we are to achieve useful reference values and standardization,
I believe high, low, and intermediate controls should be run with
each new breast case, much like laboratorians control such chemistry
tests as calcium and lactate dehydrogenase. The results of the controls
should fall within defined guidelines.
Because standardization of immunohistochemistry is not well developed,
I recommend the less expensive and equivalent proliferation index
of careful mitotic figure counting. I believe it works as well,
has as much scientific merit, and provides as much useful information.
Noel Weidner, MD
- Weidner N, Moore DH II, Ljung BM, et al. Correlation
of bromodeoxyuridine (BRDU) labeling of breast carcinoma cells
with mitotic figure content and tumor grade. Am J Surg Pathol.
1993; 17: 987–994.
- Weidner N, Moore DH II, Vartanian R. Correlation
of Ki-67 antigen expression with mitotic figure index and tumor
grade in breast carcinomas using the novel “paraffin”-reactive
MIB1 antibody. Hum Pathol. 1994;25(4):337–342.
- Mengel M, Von Wasielewski R, Wiese B, et al.
Inter-laboratory and inter-observer reproducibility of immunohistochemical
assessment of the Ki-67 labelling index in a large multi-centre
trial. JPathol. 2002; 198(3): 292–299.
Professor and Director
University of California
San Diego Medical Center
Q. What tests should we use to
diagnose recurrent spontaneous abortion? Are any treatments available
to resolve this condition?
A. Pregnancy loss typically occurs
during the second trimester in patients who have antiphospholipid
syndrome, or APS. The fetal loss rate in primary APS varies from
50 to 75 percent. Fetal loss rates are as high as 90 percent in
patients who have systemic lupus erythematosus and secondary APS.
There is a correlation between fetal loss rates and the antibody
titer, most commonly IgG anticardiolipin. IgM anticardiolipin antibodies,
however, also may play a role in recurrent spontaneous abortion.
Lupus anticoagulants should be ordered for evaluating patients with
recurrent spontaneous abortion. The Staclot LA and dilute Russell
viper venom time, or dRVVT, are the tests used by most laboratories
to identify lupus anticoagulants. IgG and IgM anticardiolipin antibodies
are also indicated.
Antibodies to β2 glycoprotein I are thought to be
significant in the pathogenesis of recurrent spontaneous abortion.
Consequently, many laboratories now incorporate an enzyme-linked
immunosorbent assay to detect antibodies to β2 GPI.
Antibodies to annexin V have also been suggested as an antigenic
target associated with recurrent spontaneous abortion.
Douglas A. Triplett, MD
- Keswani SC, Chauhan N. Antiphospholipid syndrome.
J R Soc Med. 2002; 95:336–342.
- Lockshin MD, Druzin ML. Antibody to cardiolipin
as a predictor of fetal distress or death in pregnant patients
with systemic lupus erythematosus. N Engl J Med. 1985;
- Mavragani CP, Vlachoyiannopoulos PG, et al.
Antiphospholipid syndrome: current diagnostic and therapeutic
issues. J Musculoskeletal Med. 2002; 186–193.
Professor of Pathology
Director of Medical Education
Indiana University School of Medicine
Advisor, CAP Coagulation
Q. What official accreditation
or certification of quality is offered for laboratory information
systems and laboratory information management systems?
A. Unfortunately, there is no official
organization overseeing accreditation, certification, or quality
assurance for most clinical laboratory information systems. The
notable exception is in blood banking, where the Food and Drug Administration
certifies software that handles blood donor or transfusion information.
The CAP Laboratory Accreditation Program’s laboratory general
checklist includes many items that an LIS must provide to meet fundamental
laboratory needs. There is, however, no published list of systems
meeting these criteria. CAP TODAY publishes annually a tabulation
of vendors marketing laboratory information systems, but it does
not assess the quality of these products (CAP TODAY, November 2002,
For laboratory information management systems, or LIMS, which are
used in analytic and some research laboratories, certification may
be obtained through organizations affiliated with ASTM International
or the American Society for Quality (www.asq.org).
You should contact these organizations for additional information.
Finally, some vendors of medical information systems have chosen
to become ISO-9001 certified, attesting to the general quality of
their software development processes.
Raymond D. Aller, MD
CAP TODAY Contributing Editor