November 2005
Feature Story
Significance of percentage of positive/ dissected axillary lymph nodes
in breast cancer
Micrometastasis in breast carcinoma and complete axillary dissection
BCLIO or NF-kB in predicting H. pylori-independent status of MALT
Ki67 and p53 evaluation and assessment of Barrett’s esophagusMbr
Cytologic features of high-grade SIL in conventional slides
Benign breast disease and risk of breast cancer
Significance of percentage of positive/
dissected axillary lymph nodes in breast cancer
Adjuvant therapy for women with T1-T2 breast carcinoma and one to three positive
lymph nodes is controversial due to discrepancies in reported baseline locoregional
recurrence risks. This inconsistency has been attributed to variation in lymph
node staging techniques, which have yielded different numbers of dissected lymph
nodes. The current study evaluated the prognostic impact of the percentage of
positive/dissected lymph nodes on recurrence and survival in women with one
to three positive lymph nodes. The study cohort was composed of 542 women with
pathologic T1-T2 breast carcinoma who had one to three positive lymph nodes
and who had undergone mastectomy and received adjuvant systemic therapy without
radiotherapy. Ten-year Kaplan-Meier locoregional recurrence (LRR), distant recurrence,
and overall survival rates stratified by the number of positive lymph nodes,
number of dissected lymph nodes, and percentage of positive lymph nodes were
examined using different cut-off levels. Multivariate analysis was performed
to evaluate the prognostic significance of the percentage of positive lymph
nodes in disease recurrence and survival. The median followup was 7.5 years.
Locoregional recurrence, distant recurrence, and overall survival rates correlated
significantly with the number of positive lymph nodes and the percentage of
positive lymph nodes but not with the number of dissected lymph nodes. The cut-off
level at which the most significant difference in locoregional recurrence was
observed was 25 percent positive lymph nodes. (The 10-year Kaplan-Meier locoregional
recurrence rates were 13.9 percent and 36.7 percent in women with 25 percent
or fewer and more than 25 percent positive lymph nodes, respectively; P<0.0001.)
Higher distant recurrence rates and lower overall survival rates were observed
among patients who had more than 25 percent positive lymph nodes compared with
patients who had 25 percent or fewer positive lymph nodes (distant recurrence,
53 percent versus 30.3 percent, respectively; P<0.0001; overall survival,
43.4 percent versus 62.6 percent, respectively; P<0.0001). In the multivariate
analysis, percentage of positive lymph nodes and histologic grade were significant,
independent factors associated with locoregional recurrence, distant recurrence,
and overall survival. The authors concluded that the presence of more than 25
percent positive lymph nodes was an adverse prognostic factor in patients with
one to three positive nodes and may be used to identify patients at high risk
of postmastectomy locoregional and distant recurrence who may benefit from adjuvant
radiotherapy and more aggressive systemic therapy regimens.
Truong PT, Berthelet E, Lee J, et al. The prognostic significance of the
percentage of positive/dissected axillary lymph nodes in breast cancer recurrence
and survival in patients with one to three positive axillary lymph nodes. Cancer.
2005;103:2006–2014.
Reprints: Dr. Pauline T. Truong, British Columbia Cancer Agency, Vancouver
Island Center, 2410 Lee Ave., Victoria, British Columbia, V8R 6V5, Canada; ptruong@
bccancer. bc.ca
Micrometastasis in breast carcinoma and
complete axillary dissection
The decision whether to proceed with complete axillary node dissection based
on sentinel node status is clear for patients with negative or macrometastatic
disease. However, the course of action based on sentinel node micrometastasis
remains controversial. The authors reviewed 358 cases from June 1999 to July
2003. They evaluated all sentinel nodes at three levels by frozen section, touch
preparation, and scrape preparation. Micrometastasis was defined as tumor deposits
between 0.2 mm and 2 mm. The authors recorded the size, grade, and lymphvascular
invasion of the primary tumor, as well as the number, status, and size of metastatic
disease, and presence of extranodal capsular extension of sentinel and nonsentinel
nodes. Of the 358 cases, 89 had positive sentinel nodes, 29 of which represented
micrometastases. Only one of the 29 (three percent) cases contained a nonsentinel
node with macrometastasis. In 60 of the 89 (67 percent) cases, sentinel nodes
contained macrometastases. Of these, 38 cases (63 percent) had metastatic tumor
in nonsentinel nodes. Intraoperative consult was performed in 53 of the 89 cases
with positive sentinel nodes. Only one of the 19 (five percent) intraoperative
consult cases with micrometastatic sentinel nodes had positive nonsentinel nodes,
while 21 of 34 (62 percent) of the macrometastatic sentinel nodes at intraoperative
consult had tumor in nonsentinel nodes. No single variable studied discriminated
between micro- and macrometastatic disease. At intraoperative consult, macrometastatic
disease was present in all three diagnostic preparations, while diagnostic material
in micrometastatic sentinel nodes was usually present in only one modality.
This analysis suggests that the risk of finding tumor in nonsentinel nodes differs
significantly between cases with micro- (three percent) versus macrometastatic
(63 percent) disease in sentinel nodes. This holds true for cases assessed by
intraoperative consult. Considering the known morbidity of complete axillary
dissection, the authors concluded that clinicians should assess the risk versus
benefit of undertaking this procedure on a case-by-case basis in patients with
sentinel node micrometastases.
Rutledge H, Davis J, Chiu R, et al. Sentinel node micrometastasis in breast
carcinoma may not be an indication for complete axillary dissection. Mod Pathol.
2005;18: 762–768.
Reprints: Dr. H. Rutledge, Dept. of Pathology, University of Kentucky,
Suite MS 117, 800 Rose St., Lexington KY 40536-0001; hlr1998@aol.com
BCLIO or NF-kB in predicting H. pylori-independent
status of MALT
The t(11;18)(q21;q21) translocation is a specific marker for Helicobacter pylori-independent
status of low-grade gastric lymphoma of mucosa-associated lymphoid tissue, or
MALT. However, 30 percent to 50 percent of H. pylori-independent low-grade gastric
MALT lymphomas lack this aberration. No reliable markers have been identified
to predict tumor response to H. pylori eradication in patients without the translocation.
The authors investigated whether nuclear expression of BCL10 and nuclear factor
kB, or NF-kB (found to correlate with H. pylori-independent status in gastric
high-grade MALT lymphoma), would predict H. pylori-independent status in low-grade
gastric MALT lymphomas lacking t(11;18) (q21;q21). Sixty patients who underwent
successful H. pylori-eradication for low-grade gastric MALT lymphoma were included
in the study. Forty-seven lacked t(11;18) (q21;q21). Of these, 36 were H. pylori-dependent
and 11 were H. pylori-independent. In the translocation-negative patients, nuclear
expression of BCL10 was significantly higher in H. pylori-independent than in
H. pylori-dependent tumors (72.7 percent versus 8.3 percent; P<.001). Nuclear
expression of NF-kB was also significantly higher in H. pylori-independent than
in H. pylori-dependent tumors (63.6 percent versus 8.3 percent; P<.001).
Of the 13 patients with the t(11;18) (q21;q21), 12 showed nuclear expression
of BCL10 and NF-kB. All 12 were H. pylori-independent. One case with the t(11;18)(q21;q21)
was H. pylori-dependent; it showed cytoplasmic localization of BCL10 and NF-kB.
The authors concluded that nuclear expression of BCL10 or NF-kB is predictive
of H. pylori-independent status in low-grade gastric MALT lymphomas with or
without t(11;18) (q21;q21).
Yeh KH, Kuo SH, Chen LT, et al. Nuclear expression of BCL10 or nuclear
factor kappa B helps predict Helicobacter pylori-independent status of low-grade
gastric mucosa-associated lymphoid tissue lymphomas with or without t(11;18)(q21;q21).
Blood. 2005;106(3):1037–1041.
Reprints: Ann-Lii Cheng, Dept. of Internal Medicine and Dept. of Oncology,
National Taiwan University Hospital, No. 7, Chung-Shan S Rd., Taipei, Taiwan;
andrew@ ha.mc.ntu.edu.tw; and Li-Tzong Chen, Division of Cancer Research, National
Health Research Institutes, Taipei, Taiwan; leochen@ nhri.org.tw
Ki67 and p53 evaluation and assessment of
Barrett’s esophagus
The authors conducted a study to devise clinically applicable methods for assessing
p53 and Ki67 immunohistochemical reactivity in Barrett’s esophagus and
to compare the interobserver agreement between these methods and routine hematoxylin-and-eosin
evaluation. One hundred and fifteen biopsies diagnosed as Barrett’s esophagus,
selected from the files of the University Hospital MAS, Malmö, were re-evaluated
for dysplasia by three pathologists. For immunohistochemical analysis, areas
with the most prominent positivity were evaluated. The mean of p53+ epithelial
nuclei/high-power field (HPF) was obtained by counting between one and five
HPFs per biopsy. A proliferation quotient was obtained by dividing the number
of Ki67+ epithelial nuclei in the upper half by the lower half of the mucosa
using two HPFs. Mean k values were 0.24, 0.71, and 0.52 for hematoxylin and
eosin, p53, and Ki67 evaluations, respectively. A correlation was noted between
increasing severity of dysplasia, immunohistochemical measurable overexpression
of p53, and shift of the mucosal proliferation zone towards the surface, measured
as a proliferation quotient. The authors concluded that these methods for p53
and Ki67 evaluation were more reproducible than routine hemotoxylin-and-eosin
evaluation of Barrett’s esophagus. Furthermore, the immunohistochemical
methods correlate with the severity of dysplasia and are useful supplementary
prognostic markers.
Lorinc E, Jakobsson B, Landberg G, et al. Ki67 and p53 immunohistochemistry
reduces interobserver variation in assessment of Barrett’s oesophagus.
Histopathology. 2005; 46(6):642–648.
Correspondence: Ester Lorinc, Division of Pathology, Dept. of Clinical
Pathology and Cytology, University Hospital MAS, Malmö, Sweden; ester.lorinc@skane.se
Cytologic features of high-grade SIL in
conventional slides
Previous studies have suggested that cases of high-grade squamous intraepithelial
lesion in conventional smears and in ThinPrep specimens that are frequently
misinterpreted as normal have relatively few small and hypochromatic dysplastic
cells. The authors conducted a study to determine the cytologic differences
between conventional Papanicolaou slides of high-grade squamous intraepithelial
lesion that perform poorly and those that perform well. To this end, they
compared the cytologic features of 22 cases of conventional smears with
high-grade squamous intraepithelial lesion that performed poorly in the
College of American Pathologists’ Interlaboratory Comparison Program
in Gynecologic Cytology with 45 cases of conventional smears that performed
extremely well. They found that cases that performed poorly were significantly
more likely to have 50 or fewer single dysplastic cells (P=0.003) and
to have only small dysplastic cells (P=0.01). Cases that performed well
were also more likely to have more than 500 dysplastic cells (P=0.002),
to exhibit the presence of large dysplastic cells (P<0.001), and to
be keratinized (P=0.03). Hypochromasia and the number of groups of dysplastic
cells were not correlated with performance. The authors concluded that
conventional smears with high-grade squamous intraepithelial lesion with
50 or fewer single dysplastic cells, no large dysplastic cells, and lacking
keratinization are highly associated with poor performance in this CAP
program.
Renshaw AA, Prey MU, Hodes L, et al. Cytologic features of high-grade squamous
intraepithelial lesion in conventional slides. What is the difference between
cases that perform well and those that perform poorly? Arch Pathol Lab Med.
2005;129:733–735.
Reprints: Dr. Andrew A. Renshaw, Dept. of Pathology, Baptist Hospital of
Miami, 8900 N. Kendall Drive, Miami, FL 33176-2197; andrewr@bhssf.org
Benign breast disease and risk of breast
cancer
Benign breast disease is an important risk factor for breast cancer. The authors
studied a large group of women with benign breast disease to obtain reliable
estimates of this risk. They identified all women who received a diagnosis of
benign breast disease at the Mayo Clinic between 1967 and 1991. Breast cancer
events were obtained from medical records and questionnaires. To estimate relative
risks, the authors compared the number of observed breast cancers with the number
expected on the basis of the rates of breast cancer in the Iowa Surveillance,
Epidemiology, and End Results registry. The authors followed 9,087 women for
a median of 15 years. The histologic findings were nonproliferative lesions
in 67 percent of the women, proliferative lesions without atypia in 30 percent,
and atypical hyperplasia in four percent. At the time of the study, 707 breast
cancers had developed. The relative risk of breast cancer for the cohort was
1.56 (95 percent confidence interval, 1.45 to 1.68), and this increased risk
persisted for at least 25 years after biopsy. The relative risk associated with
atypia was 4.24 (95 percent confidence interval, 3.26 to 5.41), as compared
with a relative risk of 1.88 (95 percent confidence interval, 1.66 to 2.12)
for proliferative changes without atypia and of 1.27 (95 percent confidence
interval, 1.15 to 1.41) for nonproliferative lesions. Strength of family history
of breast cancer, available for 4,808 women, was a risk factor that was independent
of histologic findings. No increased risk was found among women with no family
history of breast cancer and nonproliferative findings. In the first 10 years
after initial biopsy, an excess of cancers occurred in the same breast, especially
in women with atypia. The authors concluded that risk factors for breast cancer
after the diagnosis of benign breast disease include the histologic classification
of a benign breast lesion and family history of breast cancer.
Hartmann LC, Sellers TA, Frost MH, et al. Benign breast disease and risk
of breast cancer. N Engl J Med. 2005;353:229–237.
Reprints: Dr. L.C. Hartmann, Mayo Clinic College of Medicine, Rochester,
MN 55905
|
|
|
