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Immunohistochemistry of choriocarcinoma: an aid in differential diagnosis
Linking lymph node sampling and survival in node-negative esophageal cancer
IMP3 expression as a marker for metastatic progression and death in ccRCC
HER2 immunohistologic heterogeneous expression in core-needle biopsies
Choriocarcinoma is traditionally described as being composed of cytotrophoblast and syncytiotrophoblast. Microscopically, these two types of cells are intimately associated with each other, forming a characteristic biphasic plexiform pattern. However, the nature of these two types of trophoblastic cells is not well understood. The authors conducted a study in which they used immunohistochemistry for several trophoblastic markers to analyze the trophoblastic subpopulations in 36 gestational choriocarcinomas. They analyzed 81 specimens, including placenta, complete mole, placental site nodule, epithelioid trophoblastic tumor, and placental site trophoblastic tumor. The antibodies included Mel-CAM, HLA-G, MUC-4, and β-catenin. The authors recorded a semiquantitative assessment of positive cells and the cellular localization of these markers. They found diffuse strong membranous and cytoplasmic staining for MUC-4 in mononucleate cells in all 36 cases (100%) and a similar pattern of localization in 28 cases (78%) for HLA-G. This distribution was similar to that in normal placentas, where MUC-4 and HLA-G are expressed in the trophoblastic cells of the trophoblastic columns and implantation site. In choriocarcinoma, mononucleate trophoblastic cells showed moderate immunoreactivity for Mel-CAM, a specific marker for implantation site intermediate trophoblast, in 78 percent of the cases. The MUC-4, HLA-G, and Mel-CAM-positive trophoblastic cells were larger than cytotrophoblastic cells, with more abundant cytoplasm, consistent with the morphology of intermediate trophoblast. In contrast, 31 percent of the choriocarcinomas contained a very small proportion (<5%) of mononucleate trophoblastic cells compatible with cytotrophoblast that was positive for nuclear β-catenin, a cytotrophoblast-associated marker. These results suggest that choriocarcinoma is composed predominantly of a mixture of syncytiotrophoblast and intermediate trophoblast, with only a small proportion of cytotrophoblast. The presence of nuclear β-catenin staining in the cytotrophoblast of choriocarcinoma is consistent with the view that choriocarcinoma develops from transformed cytotrophoblastic cells that presumably are the cancer stem cells that differentiate into intermediate trophoblast or syncytiotrophoblast.
Mao TL, Kurman RJ, Huang CC, et al. Immunohistochemistry of choriocarcinoma: an aid in differential diagnosis and in elucidating pathogenesis. Am J Surg Pathol. 2007;31(11): 1726–1732.
Reprints: Dr. Ie-Ming Shih, Dept. of Pathology, Johns Hopkins Medical Institutions, 1550 Orleans St., Room 305, Baltimore, MD 21231; shihie@yahoo.com
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Lymph node metastases in esophageal cancer have important prognostic and treatment implications. However, the optimal number of nodes that should be examined for accurate staging is controversial. The authors examined the association between survival and number of lymph nodes evaluated in patients who underwent resection of lymph node-negative (American Joint Committee on Cancer TNM stage I–IIA) esophageal cancer. In their study, all patients who underwent surgery for lymph node-negative esophageal cancer between 1988 and 2003 were identified from the Surveillance, Epidemiology, and End Results cancer registry. Patients were classified into three groups based on the number of negative lymph nodes sampled during surgery (10 or less, 11 to 17, and 18 or more). Esophageal cancer-specific survival was compared among these lymph node groups using Kaplan-Meier curves. Stratified and Cox regression analyses were used to evaluate the association between survival and the number of negative nodes after adjusting for potential confounders. A total of 972 patients were included in the study. Disease-specific survival rates increased with a higher number of negative nodes. The five-year, disease-specific survival rate was 55 percent among patients with 10 or fewer negative lymph nodes, compared with 66 percent and 75 percent, respectively, for those with 11 to 17 negative nodes and 18 or more negative nodes. The number of negative lymph nodes was found to be significantly associated with survival in analyses stratified by tumor status. On multivariate regression controlling for age, race/ ethnicity, gender, histology, tumor status, and postoperative radiotherapy, a higher number of negative lymph nodes was found to be independently associated with higher disease-specific survival rates. The authors concluded that lymph node metastases in patients with esophageal cancer appear to have important prognostic and treatment implications. Data from this study suggest that patients undergoing surgical resection for esophageal cancer should have at least 18 lymph nodes removed.
Greenstein AJ, Little VR, Swanson SJ, et al. Effect of the number of lymph nodes sampled on postoperative survival of lymph node-negative esophageal cancer. Cancer. 2008:112;1239–1246.
Reprints: Dr. Juan P. Wisnivesky, Dept. of Medicine, Mount Sinai School of Medicine, 1 Gustave L. Levy Place, Box 1087, New York, NY 10029; juan.wisnivesky@mssm.edu
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The authors examined associations of the insulin-like growth factor-II mRNA binding protein (IMP3) with clinical and pathologic features of clear cell renal cell carcinoma (ccRCC) in an independent cohort of patients. The intent of their study was to validate recent work showing IMP3 as a prognostic marker for renal cell carcinoma progression and death. The authors studied 716 consecutive tumor specimens from patients treated with surgery for unilateral, sporadic, noncystic ccRCC between 1990 and 1999. Tissues were stained and scored for IMP3 expression. These expression levels were correlated with clinical and pathologic features as well as clinical outcomes, including progression to distant metastases and death from renal cell carcinoma. The authors found that 213 ccRCC specimens (29.8%) expressed tumor cell IMP3. IMP3 expression was associated with advanced stage and grade of primary tumors and other adverse features, including coagulative tumor necrosis and sarcomatoid differentiation. After multivariate adjustment for ccRCC prognostic features, positive IMP3 expression was still found to be associated with a 42 percent increase in the risk of death from renal cell carcinoma (hazards ratio, 1.42; P=.024). Among the subset of patients with clinically localized disease, positive IMP3 expression was associated with a nearly five-fold increased risk of distant metastases (HR, 4.71; P<.001). The authors concluded that tumor cell IMP3 expression is an independent predictor of aggressive ccRCC tumor behavior.
Hoffmann NE, Sheinin Y, Lohse CM, et al. External validation of IMP3 expression as an independent prognostic marker for metastatic progression and death for patients with clear cell renal cell carcinoma. Cancer. 2008;112:1471–1479.
Reprints: Dr. Eugene D. Kwon, Dept. of Urology, Mayo Clinic, 200 First Street, SW, Rochester, MN 55905; kwon.eugene@mayo.edu
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HER2 oncoprotein is overexpressed in 15 to 20 percent of breast carcinomas and is associated with poor outcome. The 2+ group is considered equivocal since gene amplification is observed in some but not others. The authors conducted a study to ascertain if there is clinical significance to heterogeneity of HER2 immunohistologic expression in breast core-needle biopsies versus surgical resection specimens. A total of 37 invasive breast carcinomas diagnosed on core-needle biopsies and scored 2+ by HER2 immunohistochemical assay were selected from the authors’ files. The results were obtained on these selected cases, of which 19 cases were nonamplified and 18 cases were amplified. The follow-up resection specimens were reviewed, and two additional tumor blocks were selected in each case for HER2 immunostaining. The 74 tissue blocks were examined for HER2 using antibody clone CB11 on the Benchmark XT and scored as negative (score, zero to 1+), weakly positive (2+), or strongly positive (3+). The authors found that in the amplified group, 56 percent (11 of 18) showed significant areas with a 3+ score in both blocks, 28 percent (five of 18) remained as 2+, and 11 percent (two of 18) showed a score of zero to 1+. In the nonamplified group, 42 percent (eight of 19) had a score of zero to 1+, 37 percent (seven of 19) remained as 2+, and none (zero of 19) had a score of 3+. Five cases showed heterogeneous staining in both groups. In the amplified group, 56 percent of cases showed strong 3+ in both blocks, of which half the cases had areas of 2+. Fluorescence in situ hybridization was performed on a representative resection specimen block. In the amplified group, 72 percent (13 of 18) of cases were amplified and 22 percent (four of 18) were nonamplified. In the nonamplified group, no amplification was detected in 89 percent (17 of 19) of cases. The authors concluded that HER2 immunohistochemistry on core-needle biopsies usually is predictive of tumor HER2 status. However, performing fluorescence in situ hybridization on core-needle biopsies almost completely resolves the issue of heterogeneous expression of HER2.
Chivukula M, Bhargava R, Brufsky A, et al. Clinical importance of HER2 immunohistologic heterogeneous expression in core-needle biopsies vs resection specimens for equivocal (immunohistochemical score 2+) cases. Mod Pathol. 2008;21:363–368.
Reprints: Dr. M. Chivukula, Dept. of Pathology, Magee-Women’s Hospital of UPMC, 300 Halket St., Pittsburgh, PA 15213; mchivukula@ mail.magee.edu
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Anatomic pathology abstracts editors: Michael Cibull, MD, professor and vice chair, Department of Pathology and Laboratory Medicine, University of Kentucky College of Medicine, Lexington; Melissa Kesler, MD, and Rouzan Karabakhtsian, MD, assistant professors of pathology and laboratory medicine, University of Kentucky College of Medicine; and Megan Zhang, MD, visiting fellow, Division of Dermatopathology, University of California, San Francisco.
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