Summary
We report a histochemical study of alkaline phosphatase (ALP) in normal cells of the female reproductive system, in pre-cancerous and cancerous lesions of the uterine cervix and in endometrial cancer to ascertain the incidence of ALP and its isoenzyme type. For this purpose, serial sections were subjected to heat stability andl-phenylalanine (LP) inhibition tests.
The Regan-like isoenzyme, a heat-stable and LP-sensitive ALP, which has been thought to derive only from cancer or the placenta, was found in uterine cervical reserve cells and endometrial luminal surface lining cells. In contrast, ALP activity in endometrial glandular cells was found to be heat and LP sensitive.
Of 183 cases of cervical neoplasia, 60 (33%) manifested non-specific ALP activity. One dysplasia and two invasive cancer cases manifested the Regan-like isoenzyme. The other 36 classifiable lesions had small-intestine ALP-like activity (marked heat and LP sensitivity) or a liver ALP-like isoenzyme (marked heat and slight LP sensitivity).
Of 42 cases of endometrial cancer, all cases manifested non-specific ALP activity. Seven endometrial cancers exhibited the Regan-like isoenzyme. The other 19 cases manifested either small intestine of liver ALP-like isoenzyme.
Our findings indicate that in the course of uterine carinogenesis, the ALP isoenzyme of reserve cell and endometrial glandular cells undergo a change and that enzyme deviation occurs.
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References
Baker, J. R. (1946) The histochemical recognition of lipine.Q. Jl microsc. Sci. 87, 441–71.
Burstone, M. S. (1958) Histochemical comparison of naphthol AS-phosphates for the demonstration of phosphatases.J. natn. Cancer Inst. 20, 601–15.
Cadeau, B. J., Blackstein, M. E. &Malkin, A. (1974) Increased incidence of placenta-like alkaline phosphatase activity in breast and genitourinary cancer.Cancer Res. 34, 729–32.
Fishman, W. H. (1973) Carcinoplacental isoenzyme antigens. InAdvances in Enzyme Regulation (edited byWeber, G.), Vol. 11, pp. 293–321. Oxford, New York: Pergamon Press.
Fishman, W. H., Inglis, N. R., Stolbach, L. L. &Krant, M. J. (1968) A serum alkaline phosphatase isoenzyme of human neoplastic cell origin.Cancer Res. 28, 150–4.
Greenstein, J. P. (1954)Biochemistry of Cancer, 2nd edn. New York: Academic Press.
Holt, S. J. (1959) Factors governing the validity of staining methods for enzymes, and their bearing upon the Gomori acid phosphatase technique.Exp. Cell Res., Suppl. 7, 1–27.
Jensen, H., Lynghye, J. &Davidsen, S. (1968) Histochemical investigation of the thermostable alkaline phosphatase in the normal full-term placenta.Acta obstet. gynec. scand. 47, 437–42.
Kellen, J. A., Bush, R. S. &Malkin, A. (1976) Placenta-like alkaline phosphatase in gynecological cancers.Cancer. Res. 36, 269–71.
Malkin, A., Kellen, J. A. &Caplan, B. (1979) The presence of placenta-like alkaline phosphatase in normal human uterine cervix and endometrium. InCarcino-Embryonic Proteins (edited byLehman, F. G.), Vol. 2, pp. 679–84. Amsterdam: Elsevier/North-Holland.
Nathanson, L. &Fishman, W. H. (1977) New observations on the Regan isoenzyme of alkaline phosphiatase in cancer patients.Cancer 27, 1388–97.
Nozawa, W., Izumi, S., Ohta, H., Shinozuka, T., Tsutsui, F., Kurihara, S. &Watanabe, K. (1975) Histochemical studies on alkaline phosphatase in uterine cervical reserve cell, precancerous and cancerous lesion. InProceedings of the 2nd Asian Cancer Conference (edited byShanmugaratnan, K.), pp. 324–6. Singapore: Stanford College Press.
Nozawa, W., Ohta, H., Izumi, S., Hayashi, S., Tsutsui, F., Kurihara, S. &Watanabe, K. (1980) Heat-stable alkaline phosphatase in normal female genital organ — With special reference to the histochemical heat-stability test andl-phenylalanine inhibition test.Acta histochem. cytochem. 13, 521–30.
Stolbach, L. L., Krant, M. J. &Fishman, W. H. (1969) Ectopic production of an alkaline phosphatase isoenzyme in patients with cancer.Ann. N.Y. Acad. Sci. 166, 760–74.
Sugimura, T., Matsushima, T., Kawachi, T., Kogure, K., Tanaka, N., Miyake, S., Hozumi, M. &Sato, H. (1972) Disdifferentiation and decarcinogenesis.Gann Monogr. Cancer Res. 13, 31–45.
Usategui-gomez, M., Yeager, F. M. &Castro, A. F. (1974) Regan isoenzyme in normal human sera.Cancer Res. 34, 2544–5.
Watanabe, K. &Fishman, W. H. (1964) Application of stereospecific inhibitor,l-phenylalamine to the enzymorphology of intestinal alkaline phosphatase.J. Histochem. Cytochem. 12, 252–60.
Watanabe, K. &Suzuki, H. (1971a) Enzyme histochemistry (Vol. II).Modern Media 17, 102–12 (in Japanese).
Watanabe, K. &Suzuki, H. (1971b) Enzyme histochemistry (Vol. 3)Modern Media 17, 149–61 (in Japanese).
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Nozawa, S., Ohta, H., Izumi, S. et al. Heat-stable alkaline phosphatase in uterine cancer, with special reference to its histochemical heat-stability and the L-phenylalanine inhibition test. Histochem J 13, 941–951 (1981). https://doi.org/10.1007/BF01002634
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DOI: https://doi.org/10.1007/BF01002634