RESUMO
The American Society of Clinical Oncology and the College of American Pathologists recommend that human epidermal growth factor receptor 2 (HER2)/neu status be determined for all invasive breast cancers. Although the most commonly used modalities to determine HER2/neu status, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), generally give concordant results, a small but consistent discordance rate between them has been demonstrated in prior studies. Most institutions in the United States use a "reflex testing strategy" for determining HER2/neu status. In a reflex testing strategy, cancers are screened with IHC, and FISH is reflexively performed only if the IHC results are classified as equivocal. Other institutions perform both tests on all cancers to maximize diagnostic accuracy (dual testing strategy). The cost-effectiveness of dual testing and reflex testing strategies are comparatively assessed herein. A decision analysis model was established comparing these 2 testing strategies. Model probabilities were obtained from an institutional invasive breast cancer cohort. Quality-adjusted life-years (QALYs) and cost estimates were extracted from published literature. All costs were converted to 2018 US$ values using the consumer price index. One-way sensitivity analysis was performed, as well as probabilistic sensitivity analyses with acceptability curves. A total of 1247 consecutive invasive breast cancer specimens were tested with a dual strategy. By IHC, 65%, 28%, and 10% were negative, equivocal, and positive, respectively. By FISH, 87% and 13% were HER2/neu-negative and HER2/neu-positive, respectively. Six patients whose cancers were IHC-positive (3+) were found to be FISH-negative. These 6 represented 5% of the 119 cases with HER2/neu 3+ scores and 0.55% of the 1082 cases with HER2/neu-negative results by FISH. Sixteen (2%) of 809 cases with a negative IHC result were ultimately classified as HER2/neu-amplified by FISH. These 16 cases constituted 10% of all cases that were ultimately classified as HER2/neu-amplified by FISH. Overall, a reflex testing strategy was found to be less costly than a dual testing strategy ($44,470.99 vs. $45,908.86, respectively), but was also less effective (10.28 vs. 10.30 QALYs). The incremental cost-effectiveness ratio was $70,051.55/QALY. In conclusion, in this single institutional cohort of breast cancers, a dual testing strategy to determine HER2/neu status was found to be more cost-effective than a reflex testing strategy.
Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama , Hibridização in Situ Fluorescente , Receptor ErbB-2/metabolismo , Adulto , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Invasividade NeoplásicaRESUMO
At some tertiary breast care centers, where many patients are referred from other institutions, it is routine to repeat testing for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2/neu) in excision specimens if these tests were performed on the preceding biopsy at the referring facility. The goal of this study is to assess the value of this practice. We documented results from ER, PR, and HER2 testing in 541 consecutive invasive breast cancers excised over a 2.5-year period and analyzed the subset (n=153) for which testing was performed on the excision specimen solely due to the fact that testing on the preceding biopsy was performed at an outside institution. The rates and directions of biopsy-to-excision change were as follows: ER [1.3% (2/153), 100% from (+) to (-)]; PR [4% (6/153), 83% from (+) to (-)]; HER2/neu assessed by immunohistochemistry [21% (29/137)]; HER2/neu assessed by fluorescence in situ hybridization [3.3% (2/61); 50% from amplified to nonamplified and 50% vice versa]. There were no ER(-) and PR(-) biopsy cases that became ER and/or PR(+) in the excision. By coordinate analysis for the hormone receptors [ie, ER and/or PR(+) being indicative of "hormone receptor" (HR) positivity], there were no cases that changed from HR(+) in the biopsy to HR(-) in the excision (or vice versa), which suggests that repeat testing for ER and PR in this setting is of limited value. In an analysis that incorporated both immunohistochemistry and in situ fluorescence hybridization results, there were 2 cases with a clinically significant biopsy-to-excision change in HER2/neu status in which that change was detected primarily because the excision was retested. These findings provide baseline data for formulating policies on whether repeat testing should routinely be performed in the described scenario.
Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/diagnóstico , Imuno-Histoquímica/métodos , Glândulas Mamárias Humanas/metabolismo , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Feminino , Humanos , Hibridização in Situ Fluorescente , Glândulas Mamárias Humanas/patologia , Programas de Rastreamento , Mastectomia , Valor Preditivo dos Testes , Prognóstico , Reprodutibilidade dos TestesRESUMO
The diagnostic distinction between endometrial serous carcinoma (ESC) and endometrial clear-cell carcinoma (CCC) may occasionally be problematic, and one potentially contributing factor is the finding of clear cells in otherwise classic cases of ESC. This study aimed to define the frequency of this finding and comparatively assessed the immunophenotype of the clear cells. A review of 56 cases of ESC identified 8 (14.28%) with clear cells, representing 1% to 20% (median 7.5) of tumoral volume in these cases. In only 3 cases were clear cells discernible at low (×20) magnification. There was no significant difference in stage distribution or age between ESC patients with and without clear cells. The immunophenotypes of ESC-associated clear cells (group 1) were compared with foci of conventional ESC on another tissue block within the same case (group 2; n = 8) as well as a randomly selected cohort of CCC cases (group 3; n = 8). Groups 1 and 2 showed no significant differences regarding p53, ER, PR, Napsin-A, p504S, and hepatocyte nuclear factor 1ß (HNF1ß) expression, or regarding mitotic indices or Ki67 proliferation rate. In contrast, group 1 cases showed an immunophenotypic profile that was notably different from that of group 3 cases, with the former showing statistically significantly higher/more frequent expression of ER, PR, Ki67, and p53 and lower/less frequent expression of Napsin-A, p504S, and HNF1ß. We conclude that clear-cell change is seen in 14% of ESCs and is discernible at low magnification in only 5%; these areas show an immunophenotype that is essentially identical to the associated background conventional ESC and are phenotypically dissimilar to CCC.
Assuntos
Adenocarcinoma de Células Claras/patologia , Biomarcadores Tumorais/análise , Cistadenocarcinoma Seroso/patologia , Neoplasias do Endométrio/patologia , Adenocarcinoma de Células Claras/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Cistadenocarcinoma Seroso/diagnóstico , Neoplasias do Endométrio/diagnóstico , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-IdadeRESUMO
Several studies have documented phenotypic alterations in breast cancer associated with neoadjuvant chemotherapy [NACT], but many of these studies are limited by the fact that they did not account for the baseline rate of expected phenotypic change between biopsies and resections in the absence of NACT. Herein, we assess whether the NACT-associated rate of phenotypic change is significantly different than would be expected in a control population of patients that did not receive NACT. From a pathologic database, we documented the estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2/neu) phenotypes of consecutive invasive breast carcinomas (n=826), as well as the subset in which at least one of these tests was assessed in both the biopsy and resection (n=340). We then compared the rates of phenotypic change in the patients that did (n=65) and did not (n=275) receive NACT. Respectively, 49.2% and 36% of the NACT and non-NACT groups showed a biopsy-to-resection change in status for at least one biomarker (p=0.0005). The NACT and non-NACT groups showed the following respective rates of a biopsy-to-resection change in phenotype: ER (9.2% vs 2.5%, p=0.02); PR (30.7% vs 8%, p=0.000006); Her2/neu-IHC (25% vs 22.3%, p=0.7), Her2/neu-FISH (7% vs 3%, p=0.6). The direction of change in the NACT group was positive in the biopsy to negative in the resection in >70% of cases for all markers. For ER and PR, there was no statistically significant difference between cases that showed a biopsy-to-excision change in phenotype and those that were more phenotypically stable regarding a wide array of clinicopathologic variables. The average percentage of ER/PR-immunoreactive tumor cells in the pre-NACT biopsies was significantly lower in the phenotypically altered cases as compared to the phenotypically stable cases. Our findings confirm that phenotypic alterations in breast cancer occur after NACT, and that these changes are more pronounced for hormone receptors (especially PR); Significant NACT-associated alterations were not apparent for HER2/neu. A distinct pathologic profile for cases displaying a phenotypic change within the NACT group was not demonstrable. The pre-NACT levels of ER and PR may affect the likelihood of a phenotypic change. These results highlight the need for repeat testing in residual tumors after NACT.
Assuntos
Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Adulto , Idoso , Biomarcadores Tumorais/análise , Quimioterapia Adjuvante , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , FenótipoRESUMO
Inverted schneiderian papillomas are rare benign tumors, most often arising from the sinonasal mucosa. We describe a case of a 59-year-old female with an inverted papilloma of the supraglottis. This is the first reported case of a supraglottic-presenting inverted papilloma. Although rare, this case demonstrates that these tumors should be considered during workup of supraglottic laryngeal masses. Laryngoscope, 127:2830-2832, 2017.