Monoclonal Mouse Anti-Human Cytokeratin, High Molecular Weight, clone 34βE12 (34βE12) is intended for laboratory use to qualitatively identify by light microscopy the 66, 57, 51 and 49kD3 proteins corresponding to cytokeratins 1, 5, 10 and 14 of the Moll catalog in acetone or methanol fixed, frozen and formalin, methacarn or Carnoy's fixed, paraffin embedded tissues. 34BE12 specifically binds to antigens located in the cytoplasm of normal squamous and ductal epithelial cells. Positive results aid in the classification of normal and abnormal cells and tissues and serve as an adjunct to conventional histopathology. The clinical interpretation of any positive staining or its absence should be complemented by morphological and histological studies with proper controls. Evaluations should be made within the context of the patient's clinical history and other diagnostic tests by a qualified individual.

Anti-Human Cytokeratin. High Molecular Weight, Clone 34BE12 Antibody may be used as one member of a panel of antibodies to aid in the differential diagnosis of anaplastic cells of undetermined origin. When used with markers of simple epithelium, it can aid in the differentiation of carcinomas from non epithelial tumors, e.g., gliomas, lymphomas, melanomas, sarcomas or seminomas. Because it does not react with all carcinomas, it may be used also as an aid in the subclassification of carcinomas. It is also useful in the differential diagnosis of small-acinar lesions of the prostate gland because it stains basal cells which are absent in the disease.

Device Description

Monoclonal Mouse Anti-Human Cytokeratin, High Molecular Weight, clone 34βE12 (Product Code No. M0630) is a mouse anti-human antibody produced as a tissue culture supernatant. The antibody is supplied in 0.05M Tris-HCl buffer, pH 7.2, containing fetal calf serum and 15mM sodium azide. (1mL total volume).
Ready-to-Use Monoclonal Mouse Anti-Human Cytokeratin, High Molecular Weight, clone 34βE12 Antibody and Negative Control (Product Code No. N1553) consists of a mouse anti-human monoclonal antibody produced as a tissue culture supernatant and pre-diluted in 0.05M Tris-HCl buffer, pH 7.6, containing fetal calf serum and 15mM sodium azide (7mL total volume). The primary antibody is packaged with a negative control reagent consisting of fetal calf serum in 0.05M Tris-HCl buffer, pH 7.6 and 15mM sodium azide (5mL total volume).

AI/ML Overview

Here's an analysis of the acceptance criteria and supporting study for the DAKO® Mouse Anti-Human Cytokeratin, High Molecular Weight, Clone 34βE12 Monoclonal Antibody (K971905), based on the provided text:

Summary of Acceptance Criteria and Device Performance (Reproducibility Study)

Acceptance Criteria	Reported Device Performance
Reproducibility	Consistent results with intra-run testing. Consistent results with inter-run testing.
Normal Tissue Staining (Positive)	Stained breast, cervix, esophagus, prostate, salivary gland, skin, thymus, and tonsil.
Normal Tissue Staining (Negative)	Did not stain adrenal, bone marrow, brain (cerebellum and cerebrum), colon, heart, kidney, liver, lung, mesothelial cells, ovary, pancreas, parathyroid, pericardium, peripheral nerve, pituitary, skeletal muscle, small intestine, spleen, stomach, testis, thyroid, and uterus.

Study Details:

Sample Size and Data Provenance for Test Set:
- Reproducibility Testing: Eight serial sections from each of three different formalin-fixed, paraffin-embedded blocks of normal skin were used. (Total: 24 sections for staining, plus 3 negative control slides per test day).
- Normal Tissue Testing: A "required panel of normal tissues" was tested. The exact number of tissue samples for each type is not specified but includes 22 different normal tissue types.
- Data Provenance: The text does not explicitly state the country of origin. The tissues were formalin-fixed and paraffin-embedded, suggesting retrospective collection typical for pathology labs.
Number of Experts and Qualifications for Ground Truth (Test Set):
- The document implies that the "Normal Tissue Testing" and "Reproducibility Testing" were observed and evaluated based on expected staining patterns. It does not explicitly state the number or qualifications of experts who established the ground truth for the test set specifically. However, the "Intended Use" section mentions that "Evaluations should be made within the context of the patient's clinical history and other diagnostic tests by a qualified individual," which suggests reliance on general pathology expertise for interpretation of staining results.
Adjudication Method for Test Set:
- "None" explicitly described. The reproducibility section mentions "consistent results," which implies agreement, but no formal adjudication process (e.g., 2+1, 3+1) is detailed. The assessment of normal tissue staining would typically be performed by a single pathologist or a pathology team without a specific adjudication mentioned in the submission.
Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
- No MRMC comparative effectiveness study was done or mentioned. This device is a diagnostic reagent (antibody) for immunohistochemistry, not an AI-assisted diagnostic tool for which such studies are typically performed.
Standalone Performance (Algorithm Only without Human-in-the-Loop):
- Not applicable. This device is a monoclonal antibody used in a laboratory setting by trained personnel; it is not an algorithm, and its performance is inherently human-dependent for interpretation.
Type of Ground Truth Used:
- Expected Immunoreactivity/Histological Norms: For normal tissue staining, the ground truth is based on established scientific knowledge of cytokeratin expression in different normal human tissues (i.e., what should stain positive and what should not).
- Reproducibility Study: The ground truth for reproducibility is the expectation that consistent staining patterns will be observed across repeated tests of the same tissue.
- Published Immunoreactivity: This section extensively cites published literature (12 articles) to support the understanding of the antibody's reactivity with various normal and neoplastic tissues. This scientific literature serves as a form of expert consensus and outcomes data on cytokeratin expression.
Sample Size for Training Set:
- Not applicable as this is not an AI/machine learning device. The design and validation of the antibody are based on biological and chemical principles, not data-driven training sets in the computational sense.
How Ground Truth for Training Set was Established:
- Not applicable. The "training" for an antibody's performance comes from its biochemical characterization and the vast body of scientific knowledge regarding cytokeratin biology and immunohistochemistry, as summarized in the "Published Immunoreactivity" section and established histological norms.

Summary

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K971905

510(k) Summary

Submitter:	DAKO Corporation6392 Via RealCarpinteria, CA 93013805-566-6655
Contact:	Gretchen M. Murray, Ph.D.
Date SummaryPrepared:	December 4, 1997DEC 12 1997
Device Name:	1) DAKO® Mouse Anti-Human Cytokeratin, High Molecular Weight, Clone34βE12. Monoclonal Antibody for Immunoenzymatic Staining (Product Code No.M0630)
	2) DAKO® Ready-to-Use Mouse Anti-Human Cytokeratin, High MolecularWeight, Clone 34βE12, Monoclonal Antibody and Negative Control Reagent forImmunoenzymatic Staining (Product Code No. N1553)
DeviceClassification:	Class I or II has been proposed for immunohistochemical staining reagents.
Panel:	The proposed device classification is under the Hematology and Pathologydevices panel, Division of Clinical Laboratory Devices.
Predicate Device:	Becton Dickinson Anti-Human Cytokeratin, CAM5.2 (FDA K864893).
DeviceDescription:	1) Monoclonal Mouse Anti-Human Cytokeratin, High Molecular Weight,clone 34βE12 (Product Code No. M0630) is a mouse anti-human antibodyproduced as a tissue culture supernatant. The antibody is supplied in 0.05M Tris-HCl buffer, pH 7.2, containing fetal calf serum and 15mM sodium azide. (1mLtotal volume).
	2) Ready-to-Use Monoclonal Mouse Anti-Human Cytokeratin, High MolecularWeight, clone 34βE12 Antibody and Negative Control (Product Code No. N1553)consists of a mouse anti-human monoclonal antibody produced as a tissue culturesupernatant and pre-diluted in 0.05M Tris-HCl buffer, pH 7.6, containing fetalcalf serum and 15mM sodium azide (7mL total volume). The primary antibody ispackaged with a negative control reagent consisting of fetal calf serum in 0.05MTris-HCl buffer, pH 7.6 and 15mM sodium azide (5mL total volume).
Intended Use:	For In Vitro Diagnostic Use
	Monoclonal mouse anti-human Cytokeratin, High Molecular Weight, clone34βE12 (34βE12) is intended for laboratory use to qualitatively identify by lightmicroscopy the 66, 57, 51 and 49kD3 proteins corresponding to cytokeratins 1, 5,10 and 14 of the Moll catalog in acetone or methanol fixed, frozen and formalin,

{1}------------------------------------------------

methacarn or Carnoy's fixed, paraffin embedded tissues. 34BE12 specifically binds to antigens located in the cytoplasm of normal squamous and ductal epithelial cells. Positive results aid in the classification of normal and abnormal cells and tissues and serve as an adjunct to conventional histopathology. The clinical interpretation of any positive staining or its absence should be complemented by morphological and histological studies with proper controls. Evaluations should be made within the context of the patient's clinical history and other diagnostic tests by a qualified individual.

Anti-Human Cytokeratin. High Molecular Weight, Clone 34BE12 Antibody may Indicated Use: be used as one member of a panel of antibodies to aid in the differential diagnosis of anaplastic cells of undetermined origin. When used with markers of simple epithelium, it can aid in the differentiation of carcinomas from non epithelial tumors, e.g., gliomas, lymphomas, melanomas, sarcomas or seminomas. Because it does not react with all carcinomas, it may be used also as an aid in the subclassification of carcinomas. It is also useful in the differential diagnosis of small-acinar lesions of the prostate gland because it stains basal cells which are absent in the disease.
Normal Tissue Testing:

The required panel of normal tissues was tested with this antibody as specified in the 3/28/95 draft of Guidance for Submissions of Immunohistochemistry applications to the FDA. All tissues were formalin fixed and paraffin embedded. Staining was performed using the DAKO LSAB®2 Peroxidase kit system (Code No. K0677).

Normal tissues exhibiting positive staining with 348E12 included the following: breast, cervix, esophagus, prostate, salivary gland, skin, thymus and tonsil. Normal tissues that did not stain with 34BE12 include adrenal, bone marrow. brain (cerebellum and cerebrum), colon. heart. kidnev, liver, lung, mesothelial cells, ovary, pancreas, parathyroid, pericardium, peripheral nerve, pituitary, skeletal muscle, small intestine. spleen, stomach, testis, thyroid and uterus.

Reproducibility Testing:

Eight serial sections from each of three different formalin-fixed, paraffin embedded blocks of normal skin were collected for testing. Testing was performed as follows:

Intra-run reproducibility: Following the standard DAKO LSAB®2 Peroxidase Kit protocol (Code No. K0677). three slides from each tissue block were stained with Ready-to-Use DAKO® Mouse Anti-Human Cytokeratin clone 34BE12 (Code No. N1553). Concurrently, one slide from each block was stained with the supplied negative control reagent.

Inter-run reproducibility: Staining one slide from each tissue block, the above procedure was repeated on two additional days. Concurrently, one slide from each block was stained with the supplied negative control reagent.

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Reproducibility experiments with 34BE12 yielded consistent results with intra- and inter-run testing. Consistent test conditions were maintained throughout the study and reagents were stored at 2-8° C. between test runs (See Section 3 for the Report of the Results of the Reproducibility Testing)

Published Immunoreactivity:

Fifteen articles published on the characterization or clinical use of high molecular weight cytokeratin were used in the submission. Eleven of those articles reported on studies using 348E12. Following is a brief summary of the compiled information.

Cytokeratins are intermediate filament cvtoskeletal proteins essential to development and differentiation of epithelial cells. Approximately twenty different cvtokeratins have been identified and are classified and numbered according to molecular weight and isoelectric points. In general, most low molecular weight cvtokeratins (40kD-54kD) are distributed in nonsquamous epithelium, Moll's Catalog numbers 7-8 and/or 17-20.2 High molecular weight cytokeratins (48kD-67kD) are found in the upper portions of the epidermis and squamous epithelium, Moll's Catalog numbers 1-6 and/or 9-16.2 The DAKO® Mouse Anti-Human Cytokeraun. High Molecular Weight, clone 34BE12 antibody has been shown to react with the 66, 57, 51 and 49kD proteins corresponding to cytokeratins 1, 5, 10 and 14 of the Moll Catalog. 134 Positive immunoreactivity with the 66. 57, 51 and 49kD antigen appears as diffuse cvtoplasmic staining and indicates cells of epithelial nature, specifically squamous or ductal epithelium.3

34BE12 reacts with a variety of normal epithelial tissue including: squamous epithelium and sweat ducts in skin. all epithelial lavers including luminal and basal epithelium and ductal cells in breast, some pneumocvtes, mesothelium and bronchial epithelium in lung, collecting duct epithelia in kidnev and ductal cells in the pancreas, bile ducts in the liver, and mesothelium and a portion of epithelium (cells with a more basal location ) of the gastrointestinal tract. Hepatocytes, pancreatic acinar cells, proximal renal tubules, and nonepithelial normal tissues are not labeled by 34BE12 4

Monoclonal antibodies to intermediate filaments can be used as an aid in the histologic subclassification of human neoplasms. The cvtoskeletal phenotype of most tumors resembles that of their normal cellular counterpart regardless of the degree of differentiation. Thus, they can be used as an aid in the differential diagnosis of anaplastic tumors of unknown origin.

It has been reported 55 that the 348E12 antibody reacted positively with high molecular weight cytokeratins present in squamous cell and ductal or transitional cell carcinomas including: squamous cell carcinoma of the skin, lung and nasopharynx, ductal carcinoma of the breast, bile duct and salivary gland as well as transitional cell carcinomas of the bladder and nasopharynx and thymomas. 348E12-negative epithelial turnors are either "acinar" type adenomas (e.g., pituitary) or adenocarcinomas of simple epithelia (e.g., endometrial carcinomas, renal and hepatocellular carcinomas) or neuroendocrine tumors.4-37 34BE12 stained epithelial mesotheliomas, but failed to react with sarcomatoid or desmoplastic mesotheliomas " Thus, 34BE12 may be used as an aid in the subclassification of carcinomas.

Even though clone 34BE12 was negative with most non epithelial turnors e.g., gliomas, lymphomas, melanomas , sarcomas or seminomas, 459 it cannot be used as the sole epithelial marker in the differential diagnosis of carcinomas from non epithelial turnors. Because it does not react with all carcinomas, another marker for simple epithelium must be incorporated into a panel of antibodies with 340E12 to aid in the differential diagnosis of anaplastic tumors of unknown origin. Epitheloid sarcomas and synovial sarcomas. however, have shown to exhibit positive staining with various cytokeratin antibodies including 34BE12.500

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It has been suggested also that 34BE12 is useful in the differential diagnosis of small acunar lesions of the It was proposed that its diagnostic value lies in the identification of basal cells. O`Malley, et. al. saw positive staining of basal cells in 47 examples of benign prostatic lesions including atypical adenomatous hyperplasia (13), basal cell hyperplasia (11), atrophy (16), post-sclerotic hyperplasia (5) and fibroepithelial nodule (2), while 21 cases of small-acinar adenocarcinomas showed no reactivity

with the antibody. This was explained as loss of basal cells in this condition. It was stressed that loss of basal cell layer is not uniform in all prostatic adenocarcinomas. Basal cells are lost only in small-acunar adenocarcinomas. It was recommended that complete absence of staining of prostate lesions with 34BE12 should be regarded as very suggestive, but not diagnostic of malignancy.

Shah et. al., 2 suggested clinical usefulness of 34BE12 as an aid in the differentiation of Paget s disease and Bowen's disease (carcinoma in situ) from Pagetoid superficial spreading melanoma. 348E12 positivity was reported in Paget's disease of the breast (5/5) and Bowen's disease (10/10). However only 1/4 of Paget s disease of the vulva stained. None of 6 of the Pagetoid superficial spreading melanomas stained.

Bibliography:

prostate gland. "

Moll R. Franke WW. Schiller DL. The Catalog of Human Cvtokeratins: Patterns of Expression in l . Normal Epithelia, Tumors and Cultured Cells. Cell 1982;31:11
1. Miettinen M. Keratin Inmunohistochemistry: Update of Applications and Pitfalls. Pathology Annuals 1993;28:113
Gown AM and Vogel AM. Monoclonal Antibodies to Intermediate Filament Proteins of Human 3. Unique and Cross-reacting Antibodies. The Journal of Cell Biology 1982;95;414 Cells:
1. Gown AM and Vogel AM. Monoclonal Antibodies to Human Intermediate Filament Proteins II. Distribution of Filaments in Normal Human Tissues. Am J Pathol 1984:114:309
1. Gown AM and Vogel AM. Monoclonal Antibodies to Human Intermediate Filament Proteins III. Analysis of Tumors. Am J Clin Pathol 1985:84:413
Dairkee SH, Puett L, Hackett AJ. Expression of Basal and Luminal Epithelium-Specific Keratins 6. in Normal, Benign and Malignant Breast Tissue. J Nat Can Inst 1988:80:691
1. Hurlimann J and Gardiol D. Immunohistochemistry in the Differential Diagnosis of Liver Carcinomas. Am J Surg Pathol 1991:15:280
8 . Bolen JW, Hammar SP, McNutt MA. Reactive and Neoplastic Serosal Tissue: A Light-Microscopic, Ultrastructural, and Immunocytochemical Study. Am J Surg Pathol 1986; 10:34
1. Bacchi CA, Zarbo RJ, Jiang JJ, Gown AM. Do Glioma Cells Express Cytokeratin? App Immunohisto 1995:3:45
1. Swanson PE, Dehner LP, Sirgi KE, Wick MR. Cytokeratin Immunoreactivity in Malignant Tumors of Bone and Soft Tissue. Appl Immunohistochem 1994;2;103
】 . O'Malley FP, Grignon DJ, Shum DT. Usefulness of Immunoperoxidase Staining with High-Molecular-Weight Cytok ratin in the Differential Diagnosis of Small-Acinar Lesions of the Prostate Gland. Virchows Archiv A Pathol Anat 1990;417:191
1. Shah KD, Tabibzadeh SS, Gerger MA. Immunohistochemical Distinction of Paget's Disease from Bowen's Disease and Superficial Spreading Melanoma with the Use of Monoclonal Cvtokeratin Antibodies. Am J Clin Pathol 1987;88:689

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/4/Picture/2 description: The image shows the logo for the Department of Health & Human Services USA. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" arranged around the perimeter. Inside the circle is a stylized image of an eagle or bird-like figure, with its wings spread upward. The image is in black and white.

Food and Drug Administration Gretchen M. Murray, Ph.D. 2098 Gaither Road Assistant Manager, Regulatory Affairs Rockville MD 20850 DAKO Corporation 6392 Via Real Carpinteria, California 93013 DEC 1 2 1997 Re : K971905/S1 Trade Name: 1.) DAKO® Mouse Anti-Human Cytokeratin, High Molecular Weight, Clone 34BE12, Monoclonal Antibody for Immunoenzymatic Staining (Product Code No. M0630).

2.) DAKO® Ready-to-Use Mouse Anti-Human Cytokeratin, High Molecular Weight, Clone 34BE12, Monoclonal Antibody and Negative Control Reagent for Immunoenzymatic Staining (Product Code No. N1553) Requlatory Class: II Product Code: DEH

Dated: September 10, 1997 Received: September 15, 1997

Dear Dr. Murray:

We have reviewed your Section 510(k) notification of intent to market the device referenced above and we have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.

If your device is classified (see above) into either class II (Special… Controls) or class III (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device -----can be found in the Code of Federal Regulations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the current Good Manufacturing Practice requirement, as set forth in the Quality System Requlation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic (QS) inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP requlation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal Laws or Requlations.

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Page 2

Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770)488-7655.

This letter will allow you to begin marketing your device as described in your 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a leqally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll free number (800) 638-2041 or at (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsmamain.html"

Sincerely yours,

Steven Butman

Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radioloqical Health

Enclosure

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K971905

510(k) Summary

Submitter:	DAKO Corporation6392 Via RealCarpinteria, CA 93013805-566-6655
Contact:	Gretchen M. Murray, Ph.D.
Date SummaryPrepared:	December 4, 1997DEC 12 1997
Device Name:	1) DAKO® Mouse Anti-Human Cytokeratin, High Molecular Weight, Clone34βE12. Monoclonal Antibody for Immunoenzymatic Staining (Product Code No.M0630)
	2) DAKO® Ready-to-Use Mouse Anti-Human Cytokeratin, High MolecularWeight, Clone 34βE12, Monoclonal Antibody and Negative Control Reagent forImmunoenzymatic Staining (Product Code No. N1553)
DeviceClassification:	Class I or II has been proposed for immunohistochemical staining reagents.
Panel:	The proposed device classification is under the Hematology and Pathologydevices panel, Division of Clinical Laboratory Devices.
Predicate Device:	Becton Dickinson Anti-Human Cytokeratin, CAM5.2 (FDA K864893).
DeviceDescription:	1) Monoclonal Mouse Anti-Human Cytokeratin, High Molecular Weight,clone 34βE12 (Product Code No. M0630) is a mouse anti-human antibodyproduced as a tissue culture supernatant. The antibody is supplied in 0.05M Tris-HCl buffer, pH 7.2, containing fetal calf serum and 15mM sodium azide. (1mLtotal volume).
	2) Ready-to-Use Monoclonal Mouse Anti-Human Cytokeratin, High MolecularWeight, clone 34βE12 Antibody and Negative Control (Product Code No. N1553)consists of a mouse anti-human monoclonal antibody produced as a tissue culturesupernatant and pre-diluted in 0.05M Tris-HCl buffer, pH 7.6, containing fetalcalf serum and 15mM sodium azide (7mL total volume). The primary antibody ispackaged with a negative control reagent consisting of fetal calf serum in 0.05MTris-HCl buffer, pH 7.6 and 15mM sodium azide (5mL total volume).
Intended Use:	For In Vitro Diagnostic Use
	Monoclonal mouse anti-human Cytokeratin, High Molecular Weight, clone34βE12 (34βE12) is intended for laboratory use to qualitatively identify by lightmicroscopy the 66, 57, 51 and 49kD3 proteins corresponding to cytokeratins 1, 5,10 and 14 of the Moll catalog in acetone or methanol fixed, frozen and formalin,

{7}------------------------------------------------

Anti-Human Cytokeratin. High Molecular Weight, Clone 34BE12 Antibody may Indicated Use: be used as one member of a panel of antibodies to aid in the differential diagnosis of anaplastic cells of undetermined origin. When used with markers of simple epithelium, it can aid in the differentiation of carcinomas from non epithelial tumors, e.g., gliomas, lymphomas, melanomas, sarcomas or seminomas. Because it does not react with all carcinomas, it may be used also as an aid in the subclassification of carcinomas. It is also useful in the differential diagnosis of small-acinar lesions of the prostate gland because it stains basal cells which are absent in the disease.
Normal Tissue Testing:

Reproducibility Testing:

Eight serial sections from each of three different formalin-fixed, paraffin embedded blocks of normal skin were collected for testing. Testing was performed as follows:

{8}------------------------------------------------

Published Immunoreactivity:

{9}------------------------------------------------

Bibliography:

prostate gland. "

Moll R. Franke WW. Schiller DL. The Catalog of Human Cvtokeratins: Patterns of Expression in l . Normal Epithelia, Tumors and Cultured Cells. Cell 1982;31:11
1. Miettinen M. Keratin Inmunohistochemistry: Update of Applications and Pitfalls. Pathology Annuals 1993;28:113
Gown AM and Vogel AM. Monoclonal Antibodies to Intermediate Filament Proteins of Human 3. Unique and Cross-reacting Antibodies. The Journal of Cell Biology 1982;95;414 Cells:
1. Gown AM and Vogel AM. Monoclonal Antibodies to Human Intermediate Filament Proteins II. Distribution of Filaments in Normal Human Tissues. Am J Pathol 1984:114:309
1. Gown AM and Vogel AM. Monoclonal Antibodies to Human Intermediate Filament Proteins III. Analysis of Tumors. Am J Clin Pathol 1985:84:413
Dairkee SH, Puett L, Hackett AJ. Expression of Basal and Luminal Epithelium-Specific Keratins 6. in Normal, Benign and Malignant Breast Tissue. J Nat Can Inst 1988:80:691
1. Hurlimann J and Gardiol D. Immunohistochemistry in the Differential Diagnosis of Liver Carcinomas. Am J Surg Pathol 1991:15:280
8 . Bolen JW, Hammar SP, McNutt MA. Reactive and Neoplastic Serosal Tissue: A Light-Microscopic, Ultrastructural, and Immunocytochemical Study. Am J Surg Pathol 1986; 10:34
1. Bacchi CA, Zarbo RJ, Jiang JJ, Gown AM. Do Glioma Cells Express Cytokeratin? App Immunohisto 1995:3:45
1. Swanson PE, Dehner LP, Sirgi KE, Wick MR. Cytokeratin Immunoreactivity in Malignant Tumors of Bone and Soft Tissue. Appl Immunohistochem 1994;2;103
】 . O'Malley FP, Grignon DJ, Shum DT. Usefulness of Immunoperoxidase Staining with High-Molecular-Weight Cytok ratin in the Differential Diagnosis of Small-Acinar Lesions of the Prostate Gland. Virchows Archiv A Pathol Anat 1990;417:191
1. Shah KD, Tabibzadeh SS, Gerger MA. Immunohistochemical Distinction of Paget's Disease from Bowen's Disease and Superficial Spreading Melanoma with the Use of Monoclonal Cvtokeratin Antibodies. Am J Clin Pathol 1987;88:689

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/10/Picture/2 description: The image shows the logo for the Department of Health & Human Services USA. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" arranged around the perimeter. Inside the circle is a stylized image of an eagle or bird-like figure, with its wings spread upward. The image is in black and white.

Dated: September 10, 1997 Received: September 15, 1997

Dear Dr. Murray:

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Page 2

Sincerely yours,

Steven Butman

Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radioloqical Health

Enclosure

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Page l of

510(k) Number (if known): K971905

Device Name: Monoclonal Mouse Anti-Human Cytokeratin, High Molecular Weight, clone 34BE12 Antibody for Immunoenzymatic Staining

Monoclonal Mouse Anti-Human Cytokeratin, High Molecular Weight, clone 34BE12 Ready-to-Use Antibody and Negative Control for Immunoenzymatic Staining

Indications For Use:

Monoclonal Mouse Anti-Human Cytokeratin, High Molecular Weight, Clone 34BE12 Antibody may be used as one member of a panel of antibodies to aid in the differential diagnosis of anaplastic cells of undetermined origin. When used with markers of simple epithelium, it can aid in the differentiation of carcinomas from non epithelial tumors, e.g., gliomas, lymphomas, melanomas, sarcomas or seminomas. Because it does not react with all carcinomas, it may be used also as an aid in the subclassification of carcinomas. It is also useful in the differential diagnosis of small-acinar lesions of the prostate gland because it stains basal cells which are absent in this disease.

The clinical interpretation of any positive staining or its absence should be complemented by morphological and histological studies with proper controls. Evaluations should be made within the context of the patient's clinical history and other diagnostic tests by a qualified individual having knowledge of all the potential antibody reactivities.

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use
(Per 21 CFR 801.109)

IVD Use
(Per 21 CFR 801.119)

(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number K971402 Format 1-2-96)

Over-The-Counter Use

Regulation Number and Section

§ 866.5550 Immunoglobulin (light chain specific) immunological test system.

(a)
Identification. An immunoglobulin (light chain specific) immunological test system is a device that consists of the reagents used to measure by immunochemical techniques both kappa and lambda types of light chain portions of immunoglobulin molecules in serum, other body fluids, and tissues. In some disease states, an excess of light chains are produced by the antibody-forming cells. These free light chains, unassociated with gamma globulin molecules, can be found in a patient's body fluids and tissues. Measurement of the various amounts of the different types of light chains aids in the diagnosis of multiple myeloma (cancer of antibody-forming cells), lymphocytic neoplasms (cancer of lymphoid tissue), Waldenstrom's macroglobulinemia (increased production of large immunoglobulins), and connective tissue diseases such as rheumatoid arthritis or systemic lupus erythematosus.(b)
Classification. Class II (performance standards).