Value of tissue microarray technology
Superficial cervicovaginal myofibroblastoma
Differentiating between the various mesenchymal proliferations in
the vulvovaginal area can be difficult and is based primarily on identifying
key clinical and morphologic features and immunoreactivity profiles.
A review of 310 mesenchymal lesions of the vaginal area and uterine
cervix from the files of the Armed Forces Institute of Pathology identified
11 cases (along with three retrieved from files at other institutions)
with similar histomorphologic features that were unique and differed
from mesodermal stromal polyp, angiomyofibroblastoma, aggressive angiomyxoma,
and other neoplasms in this region. Salient microscopic features of
this new entity include spindle and stellate mesenchymal cells of
moderate to high cellularity with variegated growth patterns embedded
in a finely collagenous stroma and separated from the mucosa by a
layer of native stroma. These tumors are further characterized by
myxoid and edematous foci, moderately increased vascularity, reactivity
for vimentin, estrogen and progesterone receptors, and desmin, reactivity
for CD34 in most, alpha-smooth-muscle actin and muscle-specific actin
in some, and no immunoreactivity for S100 protein, epithelial membrane
antigen, or keratins. Median age at incidence was 58 years (40 to
74 years), and none of the tumors recurred or metastasized following
local excision (followup, one to 20 years).
Laskin WB, Fetsch JF, Tavassoli FA. Superficial cervicovaginal
myofibroblastoma: fourteen cases of distinctive mesenchymal tumor
arising from the specialized subepithelial stroma of the lower female
genital tract. Hum Pathol. 2001;32:715-725.
Reprints: Dr. William B. Laskin, Dept. of Pathology, Northwestern
Memorial Hospital, Feinberg Pavilion 7-325, 251 E. Huron St., Chicago,
IL 60611-2908
P57KIP2 immunohistochemistry
as an adjunct in diagnosing hydatidiform mole
It is difficult to distinguish complete hydatidiform mole (CHM) from
partial hydatidiform mole (PHM) and hydropic spontaneous abortion
(SA), particularly in early gestation. The distinction, however, is
important due to the higher risk of persistent disease and choriocarcinoma
associated with CHM as compared to PHM. The authors examined p57KIP2,
a strongly paternally imprinted gene that is expressed predominantly
from the maternal allele in most tissues. Using immunohistochemistry,
they examined the expression of p57KIP2 in CMHs, which
are derived exclusively from paternal DNA; PHMs, which contain one
maternally derived and two paternally derived haploid genomes; SA;
and mature and immature placentas. Gestational age of the CHMs ranged
from five to 22 weeks and was less than 10 weeks in more than half
the cases. In 58 of 59 CHMs, expression of p57KIP2 in cytotrophoblast
and villous mesenchyme was absent or markedly decreased (focal cytotrophoblast
positivity). In contrast, expression of p57KIP2 was strong
in these tissues in normal placenta, PHM (39 of 39), and SA (51 of
51).
Castrillon DH, Sun D, Weremowicz S, et al. Discrimination of complete
hydatidiform mole from its mimics by immunohistochemistry of the paternally
imprinted gene product p57KIP2. Am J Surg Pathol.
2001;25:1225-1230.
Reprints: Dr. Diego H. Castrillon, Dept. of Pathology, Brigham
and Women’s Hospital, 75 Francis St., Boston, MA 02115; dcastrillon@partners.org
Value of tissue microarray technology
Tissue microarray technology promises to greatly expand the utility
of paraffin blocks for research, but its limitations are still being
addressed. Advances in genomics and proteomics are dramatically increasing
the need to evaluate large numbers of molecular targets for their
diagnostic, predictive, or prognostic value in clinical oncology.
Conventional molecular pathology techniques are often tedious, time-consuming,
and require a substantial amount of tissue, thereby limiting the number
of tissues and targets that can be evaluated. The authors demonstrated
the power of tissue microarray technology in analyzing prognostic
markers in 553 breast carcinomas. Four independent TMAs were constructed
by acquiring 0.6-mm biopsies from formalin-fixed, paraffin-embedded
tumors. Immunostaining of TMA sections and conventional large sections
were performed for estrogen receptor and progesterone receptor, as
well as for p53, another protein for which the data on prognostic
utility in breast cancer are less unequivocal. Compared with conventional
large- section analysis, a single sample from each tumor identified
about 95 percent of the information for estrogen receptors, 75 to
81 percent for progesterone receptors, and 70 to 74 percent for p53.
All 12 TMA analyses (three antibodies on four different arrays), however,
yielded as significant or more significant associations with tumor-specific
survival than large-section analyses (P<0.0015 for each of the 12
comparisons). A single sample from each tumor could identify associations
between molecular alterations and clinical outcome. The authors concluded
that, contrary to expectations, tissue heterogeneity did not negatively
influence the predictive power of TMA results. TMA technology will
be of substantial value in rapidly translating genomic and proteomic
information to clinical applications.
Torhorst J, Bucher C, Kononen J, et al. Tissue microarrays for
rapid linking of molecular changes to clinical endpoints. Am J
Pathol. 2001;159:2249-2256.
Reprints: Guido Sauter, Institute of Pathology, University Hospital,
Schonbeinstrasse 40, 4003 Basel, Switzerland; guido.sauter@unibas.chn