Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving fixed or stabilized – nonliving microorganism,...
Reexamination Certificate
2000-02-08
2002-01-08
Housel, James (Department: 1648)
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving fixed or stabilized, nonliving microorganism,...
C435S005000, C435S007800, C435S040510, C435S040520, C436S008000, C436S018000
Reexamination Certificate
active
06337189
ABSTRACT:
TECHNICAL FIELD
The present invention relates generally to biological specimen fixatives and more particularly to a fixative for preserving a specimen for serial or archival diagnostic examinations.
BACKGROUND ART
Exfoliative cytology is the study of cells, either naturally shed or collected, from a tissue surface. The importance of cytology as a diagnostic tool lies in the knowledge that any changes in these superficial cells can be a reflection of changes in the immediate underlying tissue. For example, the role of cytology in the field of gynecology has three important applications: (1) the detection of malignant lesions, (2) the assessment of hormone function, and (3) the identification of vaginal infections. The detection of malignant changes as early as possible in its genesis bears a direct relationship to the prognosis.
Thus, for instance, the examination of asymptomatic women for the early detection of carcinoma of the cervix is of prime importance. Carcinoma in situ is a malignant change in the cervical epithelium leaving the basement membrane unviolated, i.e., it is non-invasive. Endometrial carcinoma can also be detected cytologically, as can malignancies of the fallopian tubes, ovaries, vagina and vulva.
Diagnostic cytology has been used extensively as a detection system for alterations in cellular morphology, such as alterations which may occur when a normal cell develops into a cancerous cell. One of the main applications of diagnostic cytology is in the early detection of cervical cancer. The cervical smear and staining technique was developed by George N. Papanicolaou for detection of early neoplastic changes in the uterine cervix. In its current form, it is a necessary routine and major screening procedure for women of all ages. As such, the test has become a convenient focus for the medical profession to regularly review the health status of American women. The modem Papanicolaou (“Pap”) screening technique, is the most successful test developed for reducing the incidence of cancer of the uterine cervix.
The success rate of this screening technique is influenced by such factors as the clinical sensitivity of the screening method, that is, the false negative rate attributed by errors during sampling, screening and evaluation. In practice, although a remarkable reduction in cervical cancer has in fact occurred, this cancer has never been completely eradicated in any population ever reported, no matter how thoroughly screened. Koss, L. G. (1989), The Papanicolaou Test for Cervical Cancer Detection: A Triumph and a Tragedy, JAMA 261:737-743; see also DeMay, “Problems in Pap Smear Interpretation”, Arch. Pathol. Lab. Med. 121:229-23 (1997).
The quality of the Papanicolaou screening in the United States has received significant attention in both the public and professional sectors over the past few years. This attention has resulted in increased interest and effort from professional societies, regulatory agencies, and industry to address concerns and propose mechanisms to improve and insure the effectiveness, reliability and accuracy of the Pap screening technique. In this regard, recognition of etiologic factors in the development of cervical cancer, for example human papillomavirus (HPV) infections, may improve the sensitivity of screening programs. Morphologic assessment of such infections has potential drawbacks (“Buffered formalin is the superior fixative for the detection of HPV DNA by in situ hybridization analysis.”
Am. J. Pathol.
134:837; Tanaka, H., et al. (1993), “Patients with various types of human papillomavirus”
Cytopath.
4:273-283), with it being recognized that a sensitive method of detection would be of particular value. Chua and Hjerpe, “Polymerace Chain Reaction of Human Papillomavirus in Archival Cervical Cytology Smears,” AQCH 17(4):221-228 (1995).
Currently, the primary purpose of obtaining a specimen of cells from the cervix is for use in cytopathology to detect cervical cancer, its precursors, and other abnormalities of the reproductive tract. It would be desirable to use a sample slide preparation, such as collected for conventional cervical carcinoma cytologic screening, to perform ancillary studies to detect alterations in DNA or protein associated with carcinogenesis. A method which simultaneously permits rapid tissue fixation, excellent morphologic detail, antigen preservation without masking or denaturation, and/or which results in less RNA and DNA degradation would, therefore, be highly desirable in the diagnosis of gynecological pathologies. As those of skill in the art recognize, the specimen to be tested must also be immobilized so that it will not be damaged or released during transport for processing or during the rigorous assay procedures associated with immunocytochemical and molecular procedures.
These procedures commonly are performed on embedded or frozen tissue biopsies. Fixative type and fixation time are known to influence not only the preservation of tissue morphology (Baker, “Principles of Biological Microtechnique: A Study of Fixation and Dyeing,” 1959) and the preservation of protein antigens for immunocytochemistry (Williams, J. H., et al. (1997), “Tissue preparation for immunocytochemistry.”
J Clin. Pathol.
50:422), but also the preservation of nucleic acids for in situ hybridization (“Patients with various types of human papillomavirus”
Cytopath.
4:273-283; Weiss, L. M., and Chen, Y. Y. (1991), “Effects of different fixatives on detection of nucleic acids from paraffin-embedded tissues by in situ hybridization using oligonucleotide probes.”; “The Revised Bethesda System for Reporting Cervical/Vaginal Diagnosis: Report of the 1991 Bethesda Workshop.”
JAMA
267:1092; Nuovo, G. J., and Richart, R. M. (1989), “Buffered formalin is the superior fixative for the detection of HPV DNA by in situ hybridization analysis.”
Am. J. Pathol.
134:837; and in situ amplification (Ben-ezra, et al., Effect of Fixation on the Amplification of Nucleic Acids from Paraffin-Embedded Material by the Polymerase Chain Reaction,” J. Histochem. Cytochem. 39:351 (1991)).
The process of fixation forms the foundation for the evaluation of biological specimens on slides and for the preparation of tissue sections. For most applications, fixation preferably should prevent or arrest autolysis and putrefaction, preserve antigenic sites, preserve morphology, stabilize DNA, RNA and soluble and structural proteins, fortify the tissues against the deleterious effects of subsequent processing and facilitates staining, or a combination of some or all of these features. Biological specimens are analyzed for many purposes using a variety of different assays, including diagnostic cytology, immunocytochemistry and molecular pathology. Current methods of fixation rely on chemical agents, the most widely used being formaldehyde and alcohol.
Examples of efforts in this field include conventional aqueous bi-sulfite-based fixatives (with acetic buffer), PVP-based fixatives (with propylene glycol and methanol) as well as those outlined in U.S. Pat. No. 3,546,334 (Lerner); U.S. Pat. Nos. 4,578,282; 4,857,300 (Maksem); U.S. Pat. No. 5,104,640 (Stokes); U.S. Pat. No. 5,256,571 (Hurley); and U.S. Pat. No. 5,432,056 (Hartman et al), all of which are hereby expressly incorporated by reference. One particularly effective formulation is disclosed in U.S. Pat. No. 5,196,182 (Ryan). An example of a commercially available product is that offered by Surgipath Medical Industries, Inc. (Richmond, Ill.) under the name SURGIPATH Cytology Fixative. The latter contains ethanol, polyethylene glycol and distilled water. The polyethylene glycol generally provides a waxy coating to stop evaporation, which requires removal before slide staining. Other common exfoliative cytology fixatives include additives such as glacial acetic acid (e.g. at 3%).
In recent years, the U.S. Food and Drug Administration has approved new devices for gynecological screening, as discussed in “Finding the Proper Fit for Pap Smear Devices”, by William Check, PhD, CAP TODAY (December 1998), pp. 18 et s
Dobrusin & Thennisch PC
Foley Shanon A.
Housel James
Streck Laboratories Inc.
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