角谷 昌俊¹, 佐川 憲明¹, 富山 光広¹, 髙橋 香織², 土田 恵², 佐藤 綾子², 伴 由佳², 木村 太一³, 谷野 美智枝⁴, 山下 啓子⁵

Masatoshi KADOYA¹, Noriaki SAGAWA¹, Mitsuhiro TOMIYAMA¹, Kaori TAKAHASHI², Megumi TSUCHIDA², Ayako SATO², Yuka BAN², Taichi KIMURA³, Mishie TANINO⁴, Hiroko YAMASHITA⁵

¹江別市立病院外科, ²江別市立病院臨床検査科, ³北海道大学大学院医学研究科探索病理学講座, ⁴北海道大学大学院腫瘍病理学分野, ⁵北海道大学病院乳腺外科

¹Department of Surgery, Ebetsu City Hospital, ²Department of Clinical Laboratories, Ebetsu City Hospital, ³Department of Translational Pathology, Hokkaido University Graduate School of Medicine, ⁴Department of Cancer Pathology, Hokkaido University Graduate School of Medicine, ⁵Breast Surgery, Hokkaido University Hospital

キーワード : Sonazoid<SUP>&reg;</SUP>, contrast-enhanced ultrasound, nuclear grade, Ki67, breast cancer

目的：乳癌での造影超音波検査（contrast-enhanced ultrasound: CEUS）の染影所見とバイオマーカーの発現状況，サブタイプ，核グレード，Ki67の発現量との関係について検討した．対象と方法：2013年10月から2015年11月までに当科でCEUSを施行した乳癌手術症例45病変を対象とした．超音波造影剤Sonazoid^®を静注し，1．Bモード画像と比較した染影範囲（Bモードよりも広がる/同等/小さい），2．腫瘤内部の染影強度（周囲乳腺より強い/同等/弱い）について評価し，1，2で判定した染影範囲，染影強度とエストロゲンレセプター（estrogen receptor: ER），プロゲステロンレセプター（progesterone receptor: PgR），ヒト上皮細胞増殖因子2型（human epidermal growth factor receptor type 2: HER2），サブタイプ，核グレード，Ki67の発現量との関係について検討した．染影範囲が広がる病変では染影拡大部における組織像，同等以下の病変については染影境界部の組織像についても検討した．結果と考察：染影範囲とER，PgR，HER2発現の有無およびサブタイプとの間には関係を認めなかった．しかし，染影が広がる病変では広がらない病変と比較して，核グレードが有意に高く（χ² test. p＝0.0111），Ki67の発現量も有意に高値であった（χ² test. p＝0.0042）．一方，染影強度との関係ではいずれも相関を認めなかった．組織像の検討では，染影の広がりを示したすべての病変で，染影拡大部位にほぼ一致して周囲脂肪織への癌細胞浸潤が認められた．結論：CEUSでBモードによる腫瘍範囲よりも染影が広がる所見は，Bモードのみでは視認困難な癌細胞の周囲脂肪織への浸潤を反映しており，高い細胞増殖能を持った高悪性度の病変を示唆する所見であると考えられた．

Purpose: This study was conducted to investigate the correlation between Sonazoid^® contrast-enhanced ultrasound (CEUS) characteristics and histopathological disease parameters including biomarker expression, subtypes, nuclear grade, and Ki67 index of breast cancer. Subjects and Methods: Histopathological results from 45 patients with breast cancer who had undergone surgery after CEUS between October 2013 and November 2015 were analyzed. In terms of CEUS characteristics after bolus infusion of Sonazoid^®, enhancement size compared with the original tumor size measured by plain B-mode imaging was classified as extended, equal, and smaller size, and enhancement intensity relative to surrounding normal breast tissue was classified as high-, iso-, and hypoenhancement. The correlation between CEUS classifications and histopathological findings including estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor type 2 (HER2) expression; subtypes; nuclear grade; and Ki67 index was analyzed. Histology in the extended enhancement region in lesions with extended enhancement and that of the boundary between imaging in lesions with equal or smaller enhancement were also examined. Results and Discussion: Compared with equal or smaller enhancement, extended enhancement was significantly associated with higher nuclear grade (Chi-square test, p=0.0111) and higher Ki67 index (Chi-square test, p=0.0042). There was no significant correlation between enhancement size and ER, PgR, and HER2 expression. No histopathological finding was significantly associated with enhancement intensity. Examination of histopathological images showed that the invasion of cancer cells to peripheral adipose tissue matched the region of extended enhancement for the most part in all lesions with extended enhancement. Conclusion: Enhancement pattern in CEUS exceeding the margin of a breast cancer lesion measured by B-mode imaging reflects the invasion of cancer cells to peripheral tissue incapable of being visualized by B-mode imaging only and may suggest high grade and high proliferating potential.