- Case Report
- Open Access
A case of giant panda ovarian cancer diagnosis and histopathology
- Qi Gao†1,
- Chengdong Wang†2,
- Desheng Li2Email author,
- Hemin Zhang2,
- Linhua Deng2,
- Caiwu Li2 and
- Zhengli Chen1Email authorView ORCID ID profile
© The Author(s). 2018
- Received: 31 May 2018
- Accepted: 25 September 2018
- Published: 12 October 2018
Ovarian cancer is diagnosed clinically by detecting ovarian cancer-related factors and markers. Here, we report a case of giant panda ovarian tumor metastasis with a combination of clinical and histopathological diagnosis.
Histopathological studies revealed severe lesions and tumor cells in the ovaries, lungs, spleen, kidneys and perianal tissue. Immunohistochemistry staining showed that the ovarian cancer markers B7-H4, CA125, and HE4 were highly expressed in the lungs, kidneys, spleen, ovaries and perianal tissue. Tumor marker tests detected significantly high levels of AFP in serum.
Clinical biomarkers combined with histopathology can provide a more accurate diagnosis of ovarian cancer metastasis and identification of ovarian cancer types than either method alone. The giant panda’s death may be due to granulosa cell tumor and theca cell tumor metastasis causing multiple organ dysfunction or even failure.
- Giant panda
- Ovarian cancer
Ovarian cancer is the fifth most common cause of cancer death in women behind lung cancer, breast cancer, colorectal cancer, and pancreatic cancer . There are two major types of ovarian cancer: epithelial and germ cell neoplasms. About 90% of ovarian cancers are epithelial and develop on the surface of the ovary. These tumors are often bulky and involve both ovaries. Germ cell tumors are derived from the eggs within the ovary and, if malignant, tend to be highly aggressive .
The CA125 antigen is a high molecular weight glycoprotein that is expressed in most epithelial ovarian cancers. It is currently the favored tumor marker for epithelial ovarian cancer and has played an important role in diagnosis and incorporating the risk of a malignancy index. However, the sensitivity and specificity of CA125 is poor, and CA125 is also a valid marker for many diseases other than ovarian cancer .
Human epididymis protein 4 (HE4) is a glycoprotein that is highly expressed in ovarian cancer. It is mainly expressed in the reproductive system and in respiratory and salivary gland secretions . It has been proposed as a potential biomarker for ovarian cancer because the combination of HE4 and CA125 was more accurate than any other markers in predicting malignant ovarian tumors . The Food and Drug Administration (FDA) in U.S. has approved HE4 for monitoring the recurrence of disease in ovarian cancer patients . B7-H4, a newly identified member of the B7 family, is involved in the negative regulation of T cell-mediated immunity in peripheral tissues. Research has found that B7-H4 inhibits apoptosis and promotes tumor cell growth, adhesion, and invasion into immunodeficient systems . B7-H4 is overexpressed in ovarian cancer tissues and elevated levels are detected in the serum of ovarian cancer patients, but not in patients with benign diseases . So B7-H4 may play a more important role in tumorigenesis and metastasis. Ovarian cancer is generally diagnosed clinically by detecting ovarian cancer-related factors and markers, but the biomarker analysis alone is not sensitive enough, because the expression of related biomarker in serum can not directly reflect the extent of lesions in the tissue. So here, we report a case of giant panda ovarian tumor metastasis by combination of clinical and histopathological diagnosis. It allows us to visually understand the pathological changes in the tissue and to further diagnose the disease by detecting biomarkers.
The body of the giant panda was systematically dissected. Specimens from the heart, lungs, liver, spleen, kidneys, perianal tissue, and ovaries were fixed in 4% paraformaldehyde phosphate buffer and embedded in paraffin using routine protocols. Paraffin-embedded materials were sectioned at 5 μm for staining with H&E (hematoxylin-eosin).
Sections were dewaxed in xylene and dehydrated in alcohol and antigen retrieval was achieved by microwaving them in citrate solution for 15 min. They were then soaked in 0.3% hydrogen peroxide for 20 min to block endogenous peroxidase activity. Sections were blocked by 5% bovine serum albumin and incubated with the primary antibody against CA125 (Boiss, China), HE4 (Boiss, China) and B7-H4 (Boiss, China) at 4 °C overnight. After rinsing, a rabbit IgG SABC (StreptAvidin-Biotin Complex) immunohistochemical staining kit (Boster, China) was used according to the manufacturer’s protocols. Tissue sections were visualized with the substrate DAB (diaminobenzidine) chromogen (Boster, China). Positive results were dark blue particles, located in the cytoplasm or nucleus.
The results of routine blood examination
The results of blood biochemical examination
The test results of tumor markers in serum
Blood tests showed inflammation in the body of the giant panda, and we treated her with anti-inflammatory treatment. The giant panda was found with ligament calcification and formation of bone bridge by DR examination. Combined with her daily performance, we diagnosed her as senile with degenerative spondylitis . There is still a lack of treatment for this disease in current medical research; we could only minimize her pain with methods like massage.
Severe lesions in multiple organs were observed by histopathology. Moreover, the visible ovarian granulosa cells and theca cells become cancerous in the ovary and even transferred to the lungs, kidneys, perianal tissue and spleen. This may have severely affected the functioning of these organs. We also detected high expression of B7-HE, CA125, and HE4 by immunohistochemistry in the lungs, ovaries, kidneys, perianal tissues, and spleen. The metastasis of ovarian tumors to these areas was confirmed by the detection of ovarian cancer biomarkers in these tissues . CA125 and overexpressed AFP were also detected in serum. AFP is a tumor antigen that is expressed in cells during embryonic development and is abundantly expressed in adult tumor cells. It is useful in the clinical detection of tumor markers . There is research showing that malignant ovarian tumors include germ cells and sex cord stromal tumors, which are associated with marked elevation serum of AFP [12, 13].
Ovarian granulosa cell tumors (GCTs) are uncommon neoplasms that arise from the sex-cord stromal cells of the ovary . It has been reported that metastasis of ovarian granulosa tumor to the lung leads to structural changes and dysfunction in the lung tissue . This giant panda is diagnosed with ovarian cancer ; her death may be due to granulosa cell tumor and theca cell tumor metastasis leading to multiple organs dysfunction or even failure. In summary, clinical biomarkers combined with histopathology can provide a more accurate diagnosis of ovarian cancer metastasis and identification of ovarian cancer types. In clinical examination, in addition to detecting biomarkers of ovarian cancer in serum, it is possible to perform histopathological examination by biopsy.
We wish to thank Dr. Chengdong Wang, Dr. Desheng Li, Dr. Hemin Zhang, Dr. linhua Deng, Dr. Caiwu Li and Dr. Zhengli Chen for their technical assistance.
National Key R&D Project of China (2017YFD0501706).
National Key Technology Research and Development Program of the Ministry of Science and Technology of China (2014BAI03B01).
National Key Scientific Instrument and Equipment Development Project of China (2013YQ49085906).
Availability of data and materials
QG, ZC and CW conceived and designed the study. QG, DL, HZ, LD and CL performed the experiments. QG and CW wrote the paper. ZC revised it critically for important intellectual content the manuscript. ZC gave final approval of the version to be published. All authors read and approved the manuscript.
All protocols were approved by the animal care and use committee of Sichuan agricultural university, following the guidelines on animal experiments which come under the permit No.DY- S20174411.
Consent for publication
The authors declare that they have no competing interests.
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