【Health Lecture】How much do you know about bladder cancer tumor markers? — Urinary nuclear matrix protein (NMP22)

Bladder cancer mainly originates from malignant tumors of the transitional epithelium of the bladder. It is one of the most common malignant tumors of the urinary system and can be seen in people of all ages, with a higher incidence in men than in women. Early diagnosis of bladder cancer and appropriate treatment are of great significance to improving the prognosis of patients. The main pathological types of bladder cancer include bladder urothelial carcinoma, bladder squamous cell carcinoma, bladder adenocarcinoma, etc. Among them, the most common is bladder urothelial carcinoma, accounting for more than 90% of the total number of bladder cancer patients. The so-called bladder cancer refers to bladder urothelial carcinoma, which was previously called bladder transitional cell carcinoma. Bladder cancer is divided into non-muscle invasive bladder cancer and muscle invasive bladder cancer according to the depth of infiltration.

Causes of Bladder Cancer

The occurrence of bladder cancer is a complex, multi-factor, multi-step pathological change process, which is related to internal genetic factors, external environmental factors and gene abnormalities. Previous studies have shown that bladder cancer, like many other cancers, is caused by the activation of oncogenes and the inactivation of tumor suppressor genes. During the replication and transcription process, the damaged DNA cannot be repaired in time, affecting the cell cycle, causing cancer cells to replicate and proliferate without limit and become cancerous. The two major risk factors for the disease are smoking and long-term exposure to industrial chemical products. Smoking is currently the most confirmed risk factor for bladder cancer, which is related to the aromatic amine compound 4-aminobiphenyl contained in cigarettes.

What are the symptoms of bladder cancer?

Painless gross hematuria, blood in the urine but no pain; significantly increased frequency of urination, pain during urination and other bladder irritation symptoms, even urinary retention; there may be a tumor or tumor infiltration blocking the internal urethral opening, resulting in urinary tract obstruction, difficulty urinating or inability to urinate, long-term and severe obstruction or bilateral ureteral dilatation, water accumulation and low back pain, which can lead to renal damage and renal insufficiency when involved. Some patients do not have obvious symptoms.

Bladder cancer diagnosis techniques

Currently, the most commonly used diagnostic techniques for bladder cancer include:

(I) Urine examination: If the urine test repeatedly shows more than 5 red blood cells per high-power field of view, you should be highly alert to bladder cancer; or whether tumor cells are found.

(ii) Imaging examination: It can detect tumors larger than 0.5 cm, determine whether the bladder tumor is solitary or multiple, and determine the depth of tumor infiltration, helping doctors choose the appropriate surgical method.

(iii) Intravenous pyelography or CT reconstruction of the urinary tract: filling defects can be seen in larger tumors, and the presence of tumors in other parts of the body and their effects on the urinary tract can be detected;

(IV) Magnetic resonance imaging: such as the filling defect area of ​​the bladder, the size of the lesion, and the shape of the lesion. It can also determine the depth of tumor infiltration into the bladder wall, lymph node and visceral metastasis.

(V) Urine cytology: used to screen for bladder cancer in patients with hematuria and to review the treatment effects of bladder cancer patients. This test method can detect 40%-60% of bladder cancers, but its detection ability varies depending on the different stages, grades and locations of the tumor.

(VI) Cystoscopy: This is an effective method to directly observe the internal conditions of the bladder and perform biopsies. Although it is somewhat traumatic and uncomfortable, it is of great significance for the diagnosis and treatment of bladder tumors.

(VII) Urine bladder cancer marker: Urine nuclear matrix protein NMP22.

What is Urinary Nuclear Matrix Protein NMP22?

Nuclear matrix protein (NMP22) is an important component of the nuclear matrix. It is distributed in large quantities in urothelial cells. It constitutes the internal framework of the cell nucleus and is related to DNA replication, transcription, RNA synthesis, and the regulation of gene expression. The increase in nuclear mitotic protein is consistent with the changes in the nuclear structure/morphology of malignant cells. In tumor cells, this protein is expressed in large quantities and thus increases significantly. As cancer cells in the urinary system rupture due to apoptosis, proteins in the cells are released into the urine. Monoclonal antibodies that recognize specific regions of nuclear mitotic protein can be used to detect nuclear mitotic protein released by bladder tumor cells in urine, thereby reaching the detection level. Usually, the detection of urine NMP22 concentration is of certain value in diagnosing urethral transitional cell carcinoma.

What is the value of NMP22 in the diagnosis of bladder cancer?

It is a new marker. This test is aimed at patients with bladder cancer symptoms or bladder cancer risk factors. The standard diagnostic method is combined with this reagent method to play an auxiliary screening role in the early stage of bladder cancer patients.

(I) Screening of asymptomatic high-risk groups: Elderly people over 50 years old, especially male ≥ long-term smokers. Industrial chemical practitioners, long-distance bus drivers;

(II) Auxiliary diagnosis of clinical symptoms: hematuria, urgency, dysuria, frequent urination, urinary tract obstruction, etc.;

(III) Recurrence monitoring.

Characteristics of Urinary Nuclear Matrix Protein (NMP22)

Urinary nuclear matrix protein 22 (NMP22) is easy to detect, quick, sensitive, and easily accepted by patients. It has a good application prospect in the screening and auxiliary diagnosis of bladder cancer, and is very beneficial for the early screening of bladder cancer patients. Whether in early screening or recurrence monitoring, the sensitivity is much higher than that of urine exfoliated cells. Non-invasive diagnosis, the widely used cystoscopy is an invasive examination, which will also reduce the accuracy under inflammation or active bleeding. The non-invasive NMP22 urine test combined with cystoscopy makes doctors and patients more confident about the results of the test.

Specimen collection

Patients do not need to fast. They can collect 10-20ml of midstream urine in a sterile container for testing to avoid contamination by menstrual blood, vaginal secretions, semen, feces and other substances. Testing time: 24 hours; report time: one hour.

Does elevated NMP22 necessarily mean bladder cancer?

The normal range of NMP22 is <10U/ml. Its increase does not necessarily mean bladder cancer and cannot be diagnosed as bladder cancer. It just increases the possibility and requires close follow-up and detailed examinations, such as cystoscopy. Bladder cancer sometimes cannot detect elevated NMP22. NMP22 has high sensitivity, specificity, and positive predictive value for detecting urinary tract transitional cell carcinoma. In addition to bladder cancer, other urinary tract transitional epithelial cell carcinomas, such as urethral cancer, can also increase NMP22. Factors that may produce false positives include urinary tract infection, urinary tract stones, etc.

What should I do if I find that NMP22 is elevated?

If NMP22 is found to be elevated, medical attention should be sought promptly, and changes in NMP22 should be continuously monitored. Routine urine exfoliated cell and bladder imaging-related examinations should be requested, and interventional CT, cystoscopy, and tissue biopsy should be performed when necessary.

Image from: Qianku.com

About the Author

Cai Xiaofeng

Chief Technician of the Laboratory Department of Qinghai Provincial Hospital of Traditional Chinese Medicine

Member of the Communist Party of China. Has been engaged in laboratory work for 15 years, majoring in clinical laboratory.