Analysis of Expression of Matrix Metalloproteinases-2 and −9 in Hypopharyngeal Squamous Cell Carcinoma by in Situ Hybridization

Abstract

The gene expression of two type IV collagenases (matrix metalloproteinase [MMP]-2, a 72 kd type IV collagenase, and MMP-9, a 92 kd type IV collagenase) was investigated in carcinomas of the hypopharynx. We examined 27 cases operated on in our hospital by an in situ hybridization technique to detect their messenger RNA signals in cancer cells and surrounding stroma. Both signals were detected in all cancer nests and in stromal cells in the same specimens. Clinicopathologic studies showed a significant relationship between MMP-2 expression in the primary cancer and the outcome of treatment. Our present study suggests that hypopharyngeal squamous cell carcinoma producing MMP-2 has a high potential for invasion and metastasis and a poor outcome. The analysis of MMPs will be useful for treatment planning in hypopharyngeal carcinoma and for prognosis.

Keywords

hypopharyngeal carcinoma matrix metalloproteinase squamous cell carcinoma

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References

Hirano

Kurita

Kuratomi

Mihashi

. Carcinoma of the hypopharynx and cervical esophagus. A retrospective investigation of 67 patients. Kurume Med J 1982;29:97–111.

Tanaka

Hirano

Sato

Sanada

. Treatment of carcinoma of the hypopharynx and esophagus. B. Treatment of hypopharyngeal carcinoma. J Jpn Bronchoesophagol Soc 1992;43:88–95.

Markes

Kurnik

Powers

Ogura

. Carcinoma of the pyriform sinus. An analysis of treatment results and pattern of failure. Cancer 1978;41:1008–15.

Lam

Wei

Yuen

Lam

. Squamous cell carcinoma of the hypopharynx — analysis of treatment results. Head Neck 1993;15:405–12.

Shima

Sasaguri

Kusukawa

. Production of matrix metalloproteinase-2 and metalloproteinase-3 related to malignant behavior of esophageal carcinoma. A clinicopathologic study. Cancer 1992;70:2747–53.

Kusukawa

Sasaguri

Shima

Kameyama

Morimatsu

. Expression of matrix metalloproteinase-2 related to lymph node metastasis of oral squamous cell carcinoma. A clinicopathological study. Am J Clin Pathol 1993;99:18–23.

Pyke

Ralfkaer

Tryggvason

Dano

. Messenger RNA for two type-IV collagenases is located in stromal cell in human colon cancer. Am J Pathol 1993;142:359–65.

Chomczynski

Sacchi

. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 1987;162:156–9.

Collier

Wilhelm

Eisen

. H-ras oncogene-transformed human bronchial epithelial cells (TBE-1) secrete a single metalloproteinase capable of degrading basement membrane collagen. J Biol Chem 1988;263:6579–87.

10.

Huhtala

Tuuttila

Chow

Lohi

Keski-Oja

Tryggvason

. Complete structure of the human gene for 92-kDa type IV collagenase. J Biol Chem 1991;266:16485–90.

11.

Wilheim

Collier

Marmer

Eisen

Grant

Goldberg

. SV40-transformed human lung fibroblasts secrete a 92-kDa type IV collagenase which is identical to that secreted by normal human macrophages. J Biol Chem 1989;264:17213–21.

12.

Höltke

Kessler

. Non-radioactive labeling of RNA transcripts in vitro with the hapten digoxigenin (DIG); hybridization and ELISA-based detection. Nucleic Acids Res 1990;18:5843–51.

13.

Autio-Harmainen

Karttunen

Höyhtyä

Kauppila

Tryggvason

. Expression of 72 kilodalton type IV collagenase (gelatinase A) in benign and malignant ovarian tumor. Lab Invest 1993;69:312–21.

14.

Hermanek

Sobin

, eds. International Union Against Cancer. TNM classification of malignant tumors. 4th ed. Berlin, Germany: Springer-Verlag, 1987.

15.

Liotta

Rao

Barsky

. Tumor invasion and the extracellular matrix. Lab Invest 1983;49:636–49.

16.

Liotta

. Tumor invasion and metastasis. Role of extracellular matrix. Cancer Res 1986;46:1–7.

17.

Juarez

Clayman

Nakajima

. Role of regulation of expression of 92-kDa type-IV collagenase (MMP-9) in 2 invasive squamous-cell-carcinoma cell lines of the oral cavity. Int J Cancer 1993;55:10–8.

18.

Shima

Sasaguri

Kusukawa

. Production of matrix metalloproteinase 9 (92-kDa gelatinase) by human oesophageal squamous cell carcinoma in response to epidermal growth factor. Br J Cancer 1993;67:721–7.