CAP TODAY Pathology/Laboratory Medicine/Laboratory Management
Interrelationship of intracystic papillary carcinoma of breast with in situ and invasive carcinoma
Whether to classify intracystic papillary carcinoma as invasive or in situ ductal carcinoma is still a matter of debate. The authors conducted a study to explore the genomic relationship of this tumor to its concurrent invasive ductal carcinoma and ductal carcinoma in situ using array comparative genomic hybridization. Intracystic papillary carcinoma cases were classified into three categories: pure, with concurrent ductal carcinoma in situ, or with concurrent invasive ductal carcinoma. Each component underwent laser-capture microdissection. DNA was extracted and array comparative genomic hybridization performed. The test of difference in copy number changes among the three tumors was carried out using CGHMultiArray. Intracystic papillary carcinoma clustered with four of five concurrent ductal carcinoma in situ cases and with two of two invasive ductal carcinoma cases. Intracystic papillary carcinoma showed the highest proportions of genome copy number aberration, followed by ductal carcinoma in situ, and then by invasive ductal carcinoma (P=0.06). Comparing intracystic papillary carcinoma with invasive ductal carcinoma versus without invasive ductal carcinoma, the former had 11q22.1–23.3 loss (P=0.031) and chr5 gain (P=0.085) and was enriched with matrix metalloproteinase genes. Comparing intracystic papillary carcinoma with ductal carcinoma in situ versus without ductal carcinoma in situ, the former had gain in 5q35.3 (P=0.041), 8q24.3 (P=0.041), and 21q13.2 to 21q13.31 (P=0.011). Comparing intracystic papillary carcinoma with ductal carcinoma in situ, the latter acquired a group of genes involved in cell adhesion and motility, whereas intracystic papillary carcinoma differentially expressed genes that are involved in papillary carcinomas of other organs (thyroid and kidney). The authors concluded that the overall molecular change in intracystic papillary carcinoma is closer to ductal carcinoma in situ than to invasive ductal carcinoma, which may explain the indolent behavior of this tumor.
Khoury T, Hu Q, Liu S, et al. Intracystic papillary carcinoma of breast: interrelationship with in situ and invasive carcinoma and a proposal of pathogenesis: array comparative genomic hybridization study of 14 cases. Mod Pathol. 2014;27:194–203.
Correspondence: Dr. T. Khoury at thaer.khoury@roswellpark.org or Dr. J. Wang at jianmin.wang@roswellpark.org
Androgen-receptor expression to predict early recurrence in triple-negative breast cancer
Treatment of triple-negative invasive breast cancers, defined by the absence of estrogen and progesterone receptors and c-erbB2 expression, remains challenging. Androgen receptor, a member of the nuclear receptor superfamily involved in signaling pathways regulating cell proliferation, has been implicated in breast tumorigenesis. The authors immunohistochemically examined the expression of androgen receptor, basal markers (CK14 and 34βE12), and EGFR in 699 triple-negative invasive breast cancers in tissue microarrays using the streptavidin-biotin method. They correlated the findings with clinical outcome. Positive androgen-receptor expression was defined as staining of one percent or more of tumor cell nuclei. Survival outcomes were estimated with the Kaplan-Meier method and compared between groups with log-rank statistics. Cox proportional hazards models were used to determine the effect of androgen receptor on survival outcomes. Immunohistochemical positivity was observed in 38 percent of tumors, with the proportion of stained tumor cells ranging from one to 95 percent (mean, 29 percent; median, 10 percent). Androgen-receptor expression was inversely associated with histologic grade and mitotic score. CK14, 34βE12, and EGFR confirmed 85 percent of cases to be basal like, without significant association of basal-like phenotype with androgen-receptor expression. Disease-free survival was significantly better in androgen-receptor–positive triple-negative breast cancer, with a trend for improved overall survival. Decreased recurrence likelihood in triple-negative and basal-like tumors (hazard ratio, 0.704, 95 percent confidence interval [CI], 0.498–0.994, P=0.0464; and hazard ratio, 0.675, 95 percent CI, 0.468–0.974, P=0.0355, respectively) was noted within five years of diagnosis but not thereafter. The authors concluded that this study suggests that loss of androgen receptor in triple-negative breast cancer, including those with basal-like features, portends a worse prognosis. More work in elucidating its relationship with mechanisms of progression, as well as trials of targeted treatment for androgen receptor expressing triple-negative tumors, needs to be performed.
Thike AA, Yong-Zheng Chong L, Cheok PY, et al. Loss of androgen receptor expression predicts early recurrence in triple-negative and basal-like breast cancer. Mod Pathol. 2014;27:352–360.
Correspondence: Dr. P. H. Tan at tan.puay.hoon@sgh.com.sg
Surgical margin status in prostatectomy and risk for prostate cancer recurrence
Surgical margin status in prostatectomy is an important predictor of biochemical recurrence. The current convention is to categorize a margin as negative if tumor cells are not at the inked margin, even if they are within a few cells of the margin. The authors hypothesized that cancer within 0.1 mm of the margin confers an increased risk for biochemical recurrence (BCR). They determined the risk for BCR on the basis of surgical margin status in a cohort of 1,588 patients who underwent radical prostatectomy for prostate cancer between 1998 and 2011. Surgical margins were categorized as positive, close (less than 0.1 mm from tumor cells), or negative. Multivariate hazard ratios for BCR were determined by margin status. The authors found that of the 1,588 patients, 193 had prostate cancer recurrence. The margin status was negative in 1,058 (67 percent), close in 232 (15 percent), and positive in 298 (19 percent). Cancer that was close to the margin was a significant and independent predictor of BCR (hazard ratio, 1.53; 95 percent confidence interval [CI], 1.00–2.32) and did not differ statistically from a positive surgical margin (hazard ratio, 2.10; 95 percent CI, 1.48–2.99). The authors concluded that cancer that is within 0.1 mm of the surgical margin in prostatectomy is associated with an increased risk for prostate cancer recurrence. Patients with that margin status may be reasonable candidates for adjuvant local therapy.
Izard JP, True LD, May P, et al. Prostate cancer that is within 0.1 mm of the surgical margin of a radical prostatectomy predicts greater likelihood of recurrence. Am J Surg Pathol. 2014;38(3):333–338.
Correspondence email not provided.
Pathologic and molecular factors linked to outcome in resected GI stromal tumor
The ACOSOG (American College of Surgeons Oncology Group) Z9001 (Alliance) study, a randomized, placebo-controlled trial, demonstrated that one year of adjuvant imatinib prolonged recurrence-free survival after resection of primary gastrointestinal stromal tumor. The authors conducted a study to determine the pathologic and molecular factors associated with patient outcome. They assigned 328 patients to the placebo arm of the study and 317 to the imatinib arm. Median patient follow-up was 74 months. A total of 645 tumor specimens were available for mitotic rate or mutation analysis. The authors found that recurrence-free survival (RFS) remained superior in the imatinib arm (hazard ratio, 0.6; 95 percent confidence interval, 0.43–0.75; Cox model-adjusted P<0.001). On multivariable analysis of patients in the placebo arm, large tumor size, small bowel location, and high mitotic rate were associated with lower RFS, whereas tumor genotype was not significantly associated with such survival. Multivariable analysis of patients in the imatinib arm yielded similar findings. When comparing the two arms, imatinib therapy was associated with higher RFS in patients with a KIT exon 11 deletion of any type, but not a KIT exon 11 insertion or point mutation, KIT exon 9 mutation, PDGFRA mutation, or wild-type tumor, although some of these patient groups were small. Adjuvant imatinib did not seem to alter overall survival. The authors concluded that tumor size, location, and mitotic rate, but not tumor genotype, are associated with the natural history of gastrointestinal stromal tumor. Patients with KIT exon 11 deletions assigned to one year of adjuvant imatinib had a longer recurrence-free survival rate.
Corless CL, Ballman KV, Antonescu CR, et al. Pathologic and molecular features correlate with long-term outcome after adjuvant therapy of resected primary GI stromal tumor: the ACOSOG Z9001 trial. J Clin Oncol. 2014;32(15):1563–1570.
Correspondence: Dr. Christopher Corless at corlessc@ohsu.edun