Kits for detecting cervical dysplasia

Abstract

This invention provides methods and kits for improved diagnosis of medically relevant conditions by solution based biochemical testing procedures performed in solutions of test samples. The invention provides a method to substitute the cell based morphological information contained within the cytological and / or histological data of the test sample by molecular information obtainable from the solution, wherein the original test sample is dissolved and thus enables for accurate and reproducible assessment of medically relevant diagnosis from dissolved test samples. The method according to the invention comprises the steps of determining the levels of one or more disease markers associated with the condition to be diagnosed, determining the level of one or more normalization markers suitable to substitute the information related to morphological aspects of the sample, comparing and / or combining the data of the disease and normalization markers, and assessing diagnosis of a medically relevant condition.

Description

[0001]This application is a divisional of U.S. application Ser. No. 10 / 633,484, filed Jul. 31, 2003, which claims benefit to a foreign application, EP 02017313.4, filed Aug. 1, 2002. The contents of the above applications are incorporated herein by reference in their entirety.REFERENCE TO ELECTRONIC SEQUENCE LISTING FILE[0002]This application includes a sequence listing submitted electronically herewith as an ASCII text file named “sequence.txt”, which is 53 kB in size and was created Mar. 9, 2009; the electronic sequence listing is incorporated herein by reference in its entirety.FIELD OF THE INVENTION[0003]This invention relates to methods for performing diagnosis of medically relevant conditions by detecting the levels of relevant markers characteristic for the medically relevant condition and the levels of normalization markers. The methods pertain to characterization of the sample in a solution phase, without relying on morphological cell based information.BACKGROUND OF THE INV...

AI Technical Summary

Benefits of technology

The present invention is a method for diagnosing medical conditions such as cancer or precursory lesions by detecting the levels of relevant markers in a patient's sample solution. The method includes preparing a sample solution from the raw sample, detecting the levels of relevant markers, detecting normalization markers, and normalizing the levels of relevant markers with respect to the normalization parameters. The normalization markers can be characteristic of the presence or absence of certain cell types, differentiation patterns, or proliferation properties. The invention also includes a test kit for diagnosing a medically relevant condition.

Problems solved by technology

Thus, for examination of swabs, cytologists and pathologists have to be especially trained and even experienced examiners have a high inter- and intra-observer variance in the assessment of a diagnosis based on cytological specimens.

As a result the rate of false positive and false negative results in the screening tests remains unsatisfying high.

The morphologic examination remains laborious and time consuming and thus expensive, even when supported by the molecular methods, that make the results more reliable.

So the methods for diagnosis of conditions on a molecular level only, without the support of cell based information, are restricted to cases, where there are suitable markers, that are non-ambiguously specific for the condition to be characterized.

However, the problem with the preservation and preparation of the samples may not be overcome by just additionally using molecular markers.

This is in part due to the instability of the cell based morphological information and in part to the instability of the molecular markers to be detected during the tests.

If the samples are not prepared, transported or stored in the appropriate manner, the cell based information, or even the molecular information may get lost, or may be altered.

So the diagnosis may be impossible, or may be prone to artefacts.

For example, the interpretation of biopsies or cytological preparations is frequently made difficult or impossible because of damaged (physically or biochemically) cells.

First, the methods are highly dependent on individual perception of the examiners.

Secondly the morphological information is quite sensitive to decay processes and thus may cause artefacts after preparation of the samples.

Both aspects contribute to improper reproducibility of the results.

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