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Erschienen in: Esophagus 2/2015

01.04.2015 | Original Article

Histopathological and immunohistochemical characteristics of superficial squamous cell carcinoma forming droplet infiltration: indicator of lymph node metastasis of the esophagus

verfasst von: Ryuta Nakao, Yasuko Fujita, Nobuaki Yagi, Eiichi Konishi, Akio Yanagisawa

Erschienen in: Esophagus | Ausgabe 2/2015

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Abstract

Background

Droplet infiltration (DI) is a tumor infiltration pattern observed in superficial squamous cell carcinoma (SSCC) of the esophagus. Lymph node metastasis (LNM) is related to three reported features of DI (DILFs): longitudinal diameter ≤20 μm (DIsLF); number of constituent cells ≤4 (DInLF); distance from the primary focus ≥200 μm (DIdLF). The aim of this study was to clarify the characteristics of SSCC with high risk of LNM, by analyzing DILF-forming SSCC histopathologically and immunohistochemically.

Methods

Forty-five SSCC invading the muscularis mucosa or submucosa were divided into two groups with and without above-mentioned three DILFs. The Ki-67 labeling index (LI) and the expression of cytokeratin (CK) 13, 14, 17, and 19 were compared in the paired.

Results

The Ki-67 LI was elevated in SSCC with DIsLF and with DInLF (P < 0.001, each), but no significant difference was observed between SSCC with and without DIdLF. The expression of CK13 was decreased in SSCC with DIsLF (P < 0.01) and with DInLF (P < 0.001), but no significant difference was observed between SSCC with and without DIdLF. For CK14, CK17, and CK19, no significant difference was observed between SSCC with and without any DILF.

Conclusions

The results indicated that DIsLF and DInLF are not only LNM predictors, but useful morphological markers reflecting excessive cell proliferation, and that the reduced expression of CK13 is closely associated with DIsLF and DInLF formation at the invasive front. Therefore, the elevation of Ki-67 LI and reduced expression of CK13 suggest higher risk of LNM in esophageal SSCC.
Literatur
1.
Zurück zum Zitat Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127:2893–917.CrossRefPubMed Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127:2893–917.CrossRefPubMed
2.
Zurück zum Zitat Center for Cancer Control and Information Services. Cancer statistics in Japan-2012. Tokyo: National Cancer Center; 2012. p. 12–3. Center for Cancer Control and Information Services. Cancer statistics in Japan-2012. Tokyo: National Cancer Center; 2012. p. 12–3.
3.
Zurück zum Zitat Ozawa S, Tachimori Y, Baba H, Fujishiro M, Matsubara H, Numasaki H, et al. Comprehensive Registry of Esophageal Cancer in Japan, 2004. Esophagus. 2012;9:75–98.CrossRef Ozawa S, Tachimori Y, Baba H, Fujishiro M, Matsubara H, Numasaki H, et al. Comprehensive Registry of Esophageal Cancer in Japan, 2004. Esophagus. 2012;9:75–98.CrossRef
4.
Zurück zum Zitat Japan Esophageal Society. Japanese classification of esophageal cancer, tenth edition: part I. Esophagus. 2009;6:1–25.CrossRef Japan Esophageal Society. Japanese classification of esophageal cancer, tenth edition: part I. Esophagus. 2009;6:1–25.CrossRef
5.
Zurück zum Zitat Takahashi H, Arimura Y, Masao H, Okahara S, Tanuma T, Kodaira J, et al. Endoscopic submucosal dissection is superior to conventional endoscopic resection as a curative treatment for early squamous cell carcinoma of the esophagus (with video). Gastrointest Endosc. 2010;72:255–64.CrossRefPubMed Takahashi H, Arimura Y, Masao H, Okahara S, Tanuma T, Kodaira J, et al. Endoscopic submucosal dissection is superior to conventional endoscopic resection as a curative treatment for early squamous cell carcinoma of the esophagus (with video). Gastrointest Endosc. 2010;72:255–64.CrossRefPubMed
6.
Zurück zum Zitat Urabe Y, Hiyama T, Tanaka S, Yoshihara M, Arihiro K, Chayama K. Advantages of endoscopic submucosal dissection versus endoscopic oblique aspiration mucosectomy for superficial esophageal tumors. J Gastroenterol Hepatol. 2011;26:275–80.CrossRefPubMed Urabe Y, Hiyama T, Tanaka S, Yoshihara M, Arihiro K, Chayama K. Advantages of endoscopic submucosal dissection versus endoscopic oblique aspiration mucosectomy for superficial esophageal tumors. J Gastroenterol Hepatol. 2011;26:275–80.CrossRefPubMed
7.
Zurück zum Zitat Kodama M, Kakegawa T. Treatment of superficial cancer of the esophagus: a summary of responses to a questionnaire on superficial cancer of the esophagus in Japan. Surgery. 1998;123:432–9.CrossRefPubMed Kodama M, Kakegawa T. Treatment of superficial cancer of the esophagus: a summary of responses to a questionnaire on superficial cancer of the esophagus in Japan. Surgery. 1998;123:432–9.CrossRefPubMed
8.
Zurück zum Zitat Eguchi T, Nakanishi Y, Shimoda T, Iwasaki M, Igaki H, Tachimori Y, et al. Histopathological criteria for additional treatment after endoscopic mucosal resection for esophageal cancer: analysis of 464 surgically resected cases. Mod Pathol. 2006;19:475–80.CrossRefPubMed Eguchi T, Nakanishi Y, Shimoda T, Iwasaki M, Igaki H, Tachimori Y, et al. Histopathological criteria for additional treatment after endoscopic mucosal resection for esophageal cancer: analysis of 464 surgically resected cases. Mod Pathol. 2006;19:475–80.CrossRefPubMed
9.
Zurück zum Zitat Motoyama S, Jin M, Matsuhashi T, Nanjo H, Ishiyama K, Sato Y, et al. Outcomes of patients receiving additional esophagectomy after endoscopic resection for clinically mucosal, but pathologically submucosal, squamous cell carcinoma of the esophagus. Surg Today. 2013;43:638–42.CrossRefPubMed Motoyama S, Jin M, Matsuhashi T, Nanjo H, Ishiyama K, Sato Y, et al. Outcomes of patients receiving additional esophagectomy after endoscopic resection for clinically mucosal, but pathologically submucosal, squamous cell carcinoma of the esophagus. Surg Today. 2013;43:638–42.CrossRefPubMed
10.
Zurück zum Zitat Makuuchi H, Shimada H, Chino O, Tanaka Y, Nishi T, Oshiba G, et al. Possibility of endoscopic mucosal resection in patients with m3 and sm1 esophageal cancer (in Japanese with English abstract). Stomach Intest. 1998;33:993–1002. Makuuchi H, Shimada H, Chino O, Tanaka Y, Nishi T, Oshiba G, et al. Possibility of endoscopic mucosal resection in patients with m3 and sm1 esophageal cancer (in Japanese with English abstract). Stomach Intest. 1998;33:993–1002.
11.
Zurück zum Zitat Oyama T, Miyata Y, Simatani S, Tomori A, Hotta K, Yoshida M. Lymph nodal metastasis of m3, sm1 esophageal cancer (in Japanese with English abstract). Stomach Intest. 2002;37:71–4. Oyama T, Miyata Y, Simatani S, Tomori A, Hotta K, Yoshida M. Lymph nodal metastasis of m3, sm1 esophageal cancer (in Japanese with English abstract). Stomach Intest. 2002;37:71–4.
12.
Zurück zum Zitat Yamashina T, Ishihara R, Nagai K, Matsuura N, Matsui F, Ito T, et al. Long-term outcome and metastatic risk after endoscopic resection of superficial esophageal squamous cell carcinoma. Am J Gastroenterol. 2013;108:544–51.CrossRefPubMed Yamashina T, Ishihara R, Nagai K, Matsuura N, Matsui F, Ito T, et al. Long-term outcome and metastatic risk after endoscopic resection of superficial esophageal squamous cell carcinoma. Am J Gastroenterol. 2013;108:544–51.CrossRefPubMed
13.
Zurück zum Zitat Egashira H, Yanagisawa A, Kato Y. Predictive factors for lymph node metastasis in esophageal squamous cell carcinomas contacting or penetrating the muscularis mucosae: the utility of droplet infiltration. Esophagus. 2006;3:47–52.CrossRef Egashira H, Yanagisawa A, Kato Y. Predictive factors for lymph node metastasis in esophageal squamous cell carcinomas contacting or penetrating the muscularis mucosae: the utility of droplet infiltration. Esophagus. 2006;3:47–52.CrossRef
14.
Zurück zum Zitat Youssef EM, Matsuda T, Takada N, Osugi H, Higashino M, Kinoshita H, et al. Prognostic significance of the MIB-1 proliferation index for patients with squamous cell carcinoma of the esophagus. Cancer. 1995;76:358–66.CrossRefPubMed Youssef EM, Matsuda T, Takada N, Osugi H, Higashino M, Kinoshita H, et al. Prognostic significance of the MIB-1 proliferation index for patients with squamous cell carcinoma of the esophagus. Cancer. 1995;76:358–66.CrossRefPubMed
15.
Zurück zum Zitat Ikeda G, Isaji S, Chandra B, Watanabe M, Kawarada Y. Prognostic significance of biologic factors in squamous cell carcinoma of the esophagus. Cancer. 1999;86:1396–405.CrossRefPubMed Ikeda G, Isaji S, Chandra B, Watanabe M, Kawarada Y. Prognostic significance of biologic factors in squamous cell carcinoma of the esophagus. Cancer. 1999;86:1396–405.CrossRefPubMed
16.
Zurück zum Zitat Sasagawa H, Shiozaki A, Iitaka D, Ichikawa D, Komatsu S, Fujiwara H, et al. Ki-67 labeling index as an independent prognostic factor in human esophageal squamous cell carcinoma. Esophagus. 2012;9:195–202.CrossRef Sasagawa H, Shiozaki A, Iitaka D, Ichikawa D, Komatsu S, Fujiwara H, et al. Ki-67 labeling index as an independent prognostic factor in human esophageal squamous cell carcinoma. Esophagus. 2012;9:195–202.CrossRef
17.
Zurück zum Zitat Ohashi K, Nemoto T, Eishi Y, Matsuno A, Nakamura K, Hirokawa K. Proliferative activity and p53 protein accumulation correlate with early invasive trend, and apoptosis correlates with differentiation grade in oesophageal squamous cell carcinomas. Virchows Arch. 1997;430:107–15.CrossRefPubMed Ohashi K, Nemoto T, Eishi Y, Matsuno A, Nakamura K, Hirokawa K. Proliferative activity and p53 protein accumulation correlate with early invasive trend, and apoptosis correlates with differentiation grade in oesophageal squamous cell carcinomas. Virchows Arch. 1997;430:107–15.CrossRefPubMed
18.
Zurück zum Zitat Kawamura T, Goseki N, Koike M, Takizawa T, Endo M. Acceleration of proliferative activity of esophageal squamous cell carcinoma with invasion beyond the mucosa: immunohistochemical analysis of Ki-67 and p53 antigen in relation to histopathologic findings. Cancer. 1996;77:843–9.CrossRefPubMed Kawamura T, Goseki N, Koike M, Takizawa T, Endo M. Acceleration of proliferative activity of esophageal squamous cell carcinoma with invasion beyond the mucosa: immunohistochemical analysis of Ki-67 and p53 antigen in relation to histopathologic findings. Cancer. 1996;77:843–9.CrossRefPubMed
19.
Zurück zum Zitat Chino O, Makuuchi H, Shimada H, Machimura T, Mitomi T, Osamura RY. Assessment of the proliferative activity of superficial esophageal carcinoma using MIB-1 immunostaining for the Ki-67 antigen. J Surg Oncol. 1998;67:18–24.CrossRefPubMed Chino O, Makuuchi H, Shimada H, Machimura T, Mitomi T, Osamura RY. Assessment of the proliferative activity of superficial esophageal carcinoma using MIB-1 immunostaining for the Ki-67 antigen. J Surg Oncol. 1998;67:18–24.CrossRefPubMed
20.
Zurück zum Zitat Takahashi H, Shikata N, Senzaki H, Shintaku M, Tsubura A. Immunohistochemical staining patterns of keratins in normal oesophageal epithelium and carcinoma of the oesophagus. Histopathology. 1995;26:45–50.CrossRefPubMed Takahashi H, Shikata N, Senzaki H, Shintaku M, Tsubura A. Immunohistochemical staining patterns of keratins in normal oesophageal epithelium and carcinoma of the oesophagus. Histopathology. 1995;26:45–50.CrossRefPubMed
21.
Zurück zum Zitat Lam KY, Loke SL, Shen XC, Ma LT. Cytokeratin expression in non-neoplastic oesophageal epithelium and squamous cell carcinoma of the oesophagus. Virchows Arch. 1995;426:345–9.CrossRefPubMed Lam KY, Loke SL, Shen XC, Ma LT. Cytokeratin expression in non-neoplastic oesophageal epithelium and squamous cell carcinoma of the oesophagus. Virchows Arch. 1995;426:345–9.CrossRefPubMed
22.
Zurück zum Zitat Yamada A, Sasaki H, Aoyagi K, Sano M, Fujii S, Daiko H, et al. Expression of cytokeratin 7 predicts survival in stage I/IIA/IIB squamous cell carcinoma of the esophagus. Oncol Rep. 2008;20:1021–7.PubMed Yamada A, Sasaki H, Aoyagi K, Sano M, Fujii S, Daiko H, et al. Expression of cytokeratin 7 predicts survival in stage I/IIA/IIB squamous cell carcinoma of the esophagus. Oncol Rep. 2008;20:1021–7.PubMed
23.
Zurück zum Zitat Makino T, Yamasaki M, Takeno A, Shirakawa M, Miyata H, Takiguchi S, et al. Cytokeratins 18 and 8 are poor prognostic markers in patients with squamous cell carcinoma of the oesophagus. Br J Cancer. 2009;101:1298–306.CrossRefPubMedCentralPubMed Makino T, Yamasaki M, Takeno A, Shirakawa M, Miyata H, Takiguchi S, et al. Cytokeratins 18 and 8 are poor prognostic markers in patients with squamous cell carcinoma of the oesophagus. Br J Cancer. 2009;101:1298–306.CrossRefPubMedCentralPubMed
24.
Zurück zum Zitat Ida-Yonemochi H, Maruyama S, Kobayashi T, Yamazaki M, Cheng J, Saku T. Loss of keratin 13 in oral carcinoma in situ: a comparative study of protein and gene expression levels using paraffin sections. Mod Pathol. 2012;25:784–94.CrossRefPubMed Ida-Yonemochi H, Maruyama S, Kobayashi T, Yamazaki M, Cheng J, Saku T. Loss of keratin 13 in oral carcinoma in situ: a comparative study of protein and gene expression levels using paraffin sections. Mod Pathol. 2012;25:784–94.CrossRefPubMed
25.
Zurück zum Zitat Mikami T, Cheng J, Maruyama S, Kobayashi T, Funayama A, Yamazaki M, et al. Emergence of keratin 17 vs. loss of keratin 13: their reciprocal immunohistochemical profiles in oral carcinoma in situ. Oral Oncol. 2011;47:497–503.CrossRefPubMed Mikami T, Cheng J, Maruyama S, Kobayashi T, Funayama A, Yamazaki M, et al. Emergence of keratin 17 vs. loss of keratin 13: their reciprocal immunohistochemical profiles in oral carcinoma in situ. Oral Oncol. 2011;47:497–503.CrossRefPubMed
26.
Zurück zum Zitat Safadi RA, Musleh AS, Al-Khateeb TH, Hamasha AA. Analysis of immunohistochemical expression of k19 in oral epithelial dysplasia and oral squamous cell carcinoma using color deconvolution-image analysis method. Head Neck Pathol. 2010;4:282–9.CrossRefPubMedCentralPubMed Safadi RA, Musleh AS, Al-Khateeb TH, Hamasha AA. Analysis of immunohistochemical expression of k19 in oral epithelial dysplasia and oral squamous cell carcinoma using color deconvolution-image analysis method. Head Neck Pathol. 2010;4:282–9.CrossRefPubMedCentralPubMed
27.
Zurück zum Zitat Takashima M, Kawachi H, Yamaguchi T, Nakajima Y, Kitagaki K, Sekine M, et al. Reduced expression of cytokeratin 4 and 13 is a valuable marker for histologic grading of esophageal squamous intraepithelial neoplasia. J Med Dent Sci. 2012;59:17–28.PubMed Takashima M, Kawachi H, Yamaguchi T, Nakajima Y, Kitagaki K, Sekine M, et al. Reduced expression of cytokeratin 4 and 13 is a valuable marker for histologic grading of esophageal squamous intraepithelial neoplasia. J Med Dent Sci. 2012;59:17–28.PubMed
28.
Zurück zum Zitat Nakayama H, Mitomi H, Imamhasan A, Uchida S, Tomita N, Kajiyama Y, et al. Stepwise overexpression of p63, p53, and cytokeratin 14 during progression of esophageal squamous intraepithelial neoplasia: useful immunohistochemical markers for differential diagnosis. Esophagus. 2011;9:1–8.CrossRef Nakayama H, Mitomi H, Imamhasan A, Uchida S, Tomita N, Kajiyama Y, et al. Stepwise overexpression of p63, p53, and cytokeratin 14 during progression of esophageal squamous intraepithelial neoplasia: useful immunohistochemical markers for differential diagnosis. Esophagus. 2011;9:1–8.CrossRef
29.
Zurück zum Zitat Malecha MJ, Miettinen M. Expression of keratin 13 in human epithelial neoplasms. Virchows Arch A Pathol Anat Histopathol. 1991;418:249–54.CrossRefPubMed Malecha MJ, Miettinen M. Expression of keratin 13 in human epithelial neoplasms. Virchows Arch A Pathol Anat Histopathol. 1991;418:249–54.CrossRefPubMed
30.
Zurück zum Zitat Chu PG, Lyda MH, Weiss LM. Cytokeratin 14 expression in epithelial neoplasms: a survey of 435 cases with emphasis on its value in differentiating squamous cell carcinomas from other epithelial tumours. Histopathology. 2001;39:9–16.CrossRefPubMed Chu PG, Lyda MH, Weiss LM. Cytokeratin 14 expression in epithelial neoplasms: a survey of 435 cases with emphasis on its value in differentiating squamous cell carcinomas from other epithelial tumours. Histopathology. 2001;39:9–16.CrossRefPubMed
31.
Zurück zum Zitat Kwaspen FH, Smedts FM, Broos A, Bulten H, Debie WM, Ramaekers FC. Reproducible and highly sensitive detection of the broad spectrum epithelial marker keratin 19 in routine cancer diagnosis. Histopathology. 1997;31:503–16.CrossRefPubMed Kwaspen FH, Smedts FM, Broos A, Bulten H, Debie WM, Ramaekers FC. Reproducible and highly sensitive detection of the broad spectrum epithelial marker keratin 19 in routine cancer diagnosis. Histopathology. 1997;31:503–16.CrossRefPubMed
32.
Zurück zum Zitat Troyanovsky SM, Guelstein VI, Tchipysheva TA, Krutovskikh VA, Bannikov GA. Patterns of expression of keratin 17 in human epithelia: dependency on cell position. J Cell Sci. 1989;93(Pt 3):419–26.PubMed Troyanovsky SM, Guelstein VI, Tchipysheva TA, Krutovskikh VA, Bannikov GA. Patterns of expression of keratin 17 in human epithelia: dependency on cell position. J Cell Sci. 1989;93(Pt 3):419–26.PubMed
33.
Zurück zum Zitat Roh MS, Lee JI, Choi PJ. Tumor budding as a useful prognostic marker in esophageal squamous cell carcinoma. Dis Esophagus. 2004;17:333–7.CrossRefPubMed Roh MS, Lee JI, Choi PJ. Tumor budding as a useful prognostic marker in esophageal squamous cell carcinoma. Dis Esophagus. 2004;17:333–7.CrossRefPubMed
34.
Zurück zum Zitat Koike M, Kodera Y, Itoh Y, Nakayama G, Fujiwara M, Hamajima N, et al. Multivariate analysis of the pathologic features of esophageal squamous cell cancer: tumor budding is a significant independent prognostic factor. Ann Surg Oncol. 2008;15:1977–82.CrossRefPubMed Koike M, Kodera Y, Itoh Y, Nakayama G, Fujiwara M, Hamajima N, et al. Multivariate analysis of the pathologic features of esophageal squamous cell cancer: tumor budding is a significant independent prognostic factor. Ann Surg Oncol. 2008;15:1977–82.CrossRefPubMed
35.
Zurück zum Zitat Nakanishi Y, Ohara M, Doumen H, Kimura N, Ishidate T, Kondo S. Correlation between tumor budding and post-resection prognosis in patients with invasive squamous cell carcinoma of the thoracic esophagus. World J Surg. 2011;35:349–56.CrossRefPubMed Nakanishi Y, Ohara M, Doumen H, Kimura N, Ishidate T, Kondo S. Correlation between tumor budding and post-resection prognosis in patients with invasive squamous cell carcinoma of the thoracic esophagus. World J Surg. 2011;35:349–56.CrossRefPubMed
Metadaten
Titel
Histopathological and immunohistochemical characteristics of superficial squamous cell carcinoma forming droplet infiltration: indicator of lymph node metastasis of the esophagus
verfasst von
Ryuta Nakao
Yasuko Fujita
Nobuaki Yagi
Eiichi Konishi
Akio Yanagisawa
Publikationsdatum
01.04.2015
Verlag
Springer Japan
Erschienen in
Esophagus / Ausgabe 2/2015
Print ISSN: 1612-9059
Elektronische ISSN: 1612-9067
DOI
https://doi.org/10.1007/s10388-014-0459-z

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