Annals of Diagnostic Pathology 20 (2016) 36–39

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Annals of Diagnostic Pathology

Aberrant 7 and 20 expression in triple-negative carcinoma of the breast

Hajime Kuroda, MD a,b,⁎, Yasuo Imai, MD b, Hidetsugu Yamagishi, MD b, Yoshihiko Ueda, MD c, Kazuko Kuroso, MD c,YokoOishi,MDd, Hitoshi Ohashi, MD e, Akinori Yamashita, MD e, Yoshiko Yashiro, MD e, Hisaki Fukushima, MD e a Department of Pathology, International University of Health and Welfare Hospital, Tochigi, Japan b Department of Diagnostic Pathology, Dokkyo Medical University, Tochigi, Japan c Department of Pathology, Dokkyo Medical University Koshigaya Hospital, Saitama, Japan d Department of Breast Surgery, Nissan Tamagawa Hospital, Setagaya Ward, Tokyo, Japan e Department of Breast Surgery, International University of Health and Welfare Hospital, Tochigi, Japan article info abstract

Keywords: Early studies characterizing the keratin (K) profile of various epithelial tissues indicated that breast carcinoma is Keratin 7 K7 positive and K20 negative, but not all breast carcinomas show this profile. Triple-negative carcinoma (TNC) has been characterized by negativity for estrogen receptor (ER), progesterone receptor (PgR), and Her2/neu pro- Triple-negative carcinoma, breast carcinoma tein. TNC is more likely to metastasize to the viscera and present as a metastatic poorly different carcinoma. In our study, on the basis of immunohistochemical staining of ER, PgR, and Her2/neu, 75 of the 290 patients with inva- sive breast carcinoma were judged to have TNC. K20 expression was detected in 6 of 75 patients with TNC, and non-TNC was negative in all 215 cases (P = .0003). K7 expression was also detected in 72 of 75 TNC cases. How- ever, non-TNC was negative in 26 of 215 cases, which was significant (P = .0457). An aberrant profile of K was observed in the TNC group, indicating that caution is needed in determining the site of primary tumors using im- munohistochemical algorithms. It should be kept in mind that patients with TNC show highly variable K profiles in practical diagnosis. © 2015 Elsevier Inc. All rights reserved.

1. Introduction receptor (ER), progesterone receptor (PgR), and Her2/neu [21–30]. Triple-negative carcinomas tend to exhibit rapid growth and (Ks) are the intermediate filament characteristically often present as large masses, occur more frequently in young women, found in and epithelial tumors [1,2]. Expressions of these dif- and are associated with a poor prognosis [21–38]. Importantly, they are ferent Ks are distributed in a more or less tissue-specific manner, as sug- more likely to metastasize to the viscera (lung and brain) and present gested by early immunohistochemical studies [3,4]. Most importantly, the as a metastatic poorly different carcinoma [20,29,30]. Kprofile of a particular carcinoma has proven to be a useful aid in the dif- In this study, our aim was to analyze the expression frequency and ferential diagnosis of carcinomas, because studies have shown that tu- pattern of positivity of commonly used antibodies (K7 and K20) in breast mors tend to express the K profiles of the epithelium from which they carcinoma.ThetumorsweresubcategorizedonthebasisofER,PgR,and originated [5–11]. Several early studies indicated that the breast carcino- Her2/neu immunostaining to determine whether either group was asso- ma profile is keratin 7 (K7) positive and keratin 20 (K20) negative ciated with a specific staining pattern when using these Ks. (Table 1) [12–20]. On the basis of the clinical behavior, histological differ- ence, and expression profiling, breast carcinoma is not a single dis- ease [21–38]. Therefore, not all breast carcinomas show this profile, 2. Materials and methods which was examined in a relatively small number of samples. Despite such limitations, the results of these studies are used widely in daily clin- The patients included in this study were 290 patients with primary ical practice in cases with an unknown primary origin. Triple-negative invasive breast carcinoma who were treated at the International Uni- carcinoma (TNC) has been characterized by negativity for estrogen versity of Health and Welfare Hospital, Dokkyo Medical University Ko- shigaya Hospital, and Nissan Tamagawa Hospital. Clinical information was extracted from the medical records. Pathological diagnoses were ⁎ Corresponding author at: Department of Pathology, International University of Health and Welfare Hospital, 537–3 Iguchi, Nasushiobara, Tochigi 329–2763, Japan. assigned retrospectively according to the criteria adopted by the E-mail address: [email protected] (H. Kuroda). World Health Organization classification [39]. http://dx.doi.org/10.1016/j.anndiagpath.2015.10.007 1092-9134/© 2015 Elsevier Inc. All rights reserved. H. Kuroda et al. / Annals of Diagnostic Pathology 20 (2016) 36–39 37

Table 1 K7 and K20 expressions in breast carcinoma reported in the literature.

Article No. Types of breast carcinoma K7-positive cases K20-positive cases

Ramaekers et al [12] 80 Not specified 70 NA Moll et al [13] 146 IC NST, ILC, medullary, and mucinous NA 1 Wang et al [14] 49 IC NST and ILC 48 8 Malzahn et al [15] 101 IC NST 90 3 Tot et al [16] 123 Special type only 120 10 Lagendijk et al [17] 43 IC NST, ILC, and medullary 40 8 Tot et al [18] 79 ILC 75 2 Chu et al [19] 26 IC NST and ILC 25 0 Davion et al [20] 136 TNC 132 6 Current 290 IC NST, special types, and TNC 261 4

Abbreviation: IC NST, invasive carcinoma of NST; NA, not assessed.

3. Results 2.1. Two hundred ninety breast carcinomas were selected; 243 invasive Sufficient lumpectomy specimens of breast diseases remained in carcinomas of no special type (NST), and special types (8 invasive lobu- blocks to permit the cutting of additional sections for immunohistochem- lar carcinoma [ILC], 6 medullary carcinoma, 11 mucinous carcinoma, 8 ical staining. Specimens were judged to be positive for ER (clone SP1) or invasive micropapillary carcinoma, 5 carcinoma with neuroendocrine PgR (clone A9621A) when at least 1% of the nuclei in the tumor cells features, 3 apocrine carcinoma, 2 tubular carcinoma, 2 glycogen-rich stained positively. Tumor cells were considered positive for Her2/neu clear cell carcinoma, 1 tubulolobular carcinoma, and 1 spindle cell carci- protein (clone SV2-61γ) overexpression when more than 30% of the noma) (Table 2). All patients were women, and their ages ranged from cells showed strong membrane staining (equivalent to a score of 3+). 28 to 96 years (mean, 61). The mean tumor size was 2.2 cm at the max- On the basis of these results, TNC were selected from patients with inva- imum diameter. The Elston and Ellis–modified Bloom-Richardson sive breast carcinoma. K7 (clone OV-TL 12/30) and K20 (clone Ks20.8) grades were I and II in 169 cases, and grade III in 121 cases. Trends be- were evaluated by immunohistochemical analysis using Nichirei antibod- tween the K status and age, tumor size, nodal metastasis, and tumor ies (Nichirei Biosciences Inc), respectively (Figs. 1 and 2). Briefly, 5-μm- grade were examined in breast carcinoma. However, these were not sig- thick, unstained sections were placed onto an electrostatically charged nificant (Table 2). glass slide and baked to allow for tissue adherence. The sections were On immunohistochemical staining of ER, PgR, and Her2/neu, 75 deparaffinized and rehydrated in graded alcohol. For antigen retrieval, breast carcinoma patients were judged to have TNC. Patients with TNC the sections were incubated with protease for 10 min in chambers at were, on average, younger than those with non-TNC (mean age, 58 vs 37°C. The sections were then taken to an automated stainer (Nichirei, 61.3 years, respectively), but this difference was not significant. More- Histostainer 36A) following the vendor's protocol. Cases were considered over, the mean tumor size did not differ between TNC and non-TNC K7 and K20 positive if any cytoplasmic staining was observed in the can- (mean tumor size, 2.6 vs 2.2 cm, respectively). Of note, TNC cases in- cer cells, even if focal. All immunohistochemical markers were prediluted cluded high rates of nodal metastasis and grade III tumors that distin- by the vendor. guished them from the non-TNC cases (Table 3). The frequencies of K7 and K20 expression are summarized in Tables 2 2.2. Statistical analysis and 4. K7 and K20 positivity was generally diffuse and cytoplasmic. Most cases were positive for K7 (261 of 290 cases, 90.0%). In contrast, The χ2 test was used to assess associations among variables, and only a small number of cases were K20 positive (4 of 290 cases, 13.8%). Mann-Whitney test was used to compare means of clinical data. The as- TNC was K7 positive in 72 (96.0%) of 75 cases, and non-TNC was sociations of expressions of K7 and K20 were analyzed using the χ2 test positive in 189 (87.9%) of 215 cases (P = .0457). K20 expression was de- and Fisher exact test to assess whether there were significant differ- tected in 6 (8.0%) of 75 TNC cases, and non-TNC was negative in all 215 ences in expression. Differences were considered significant when P cases (P = .003). was less than .05.

Fig. 1. Breast carcinoma with strong and diffuse cytoplasmic reactivity of tumor cells to the Fig. 2. Carcinoma with focal and weak cytoplasmic reactivity of tumor cells to the K20 an- K7 antibody scored as positive (×100). tibody scored as positive (×100). Download English Version: https://daneshyari.com/en/article/4129739

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