Weihua Tang

Heparanase: a key enzyme in invasion and metastasis of gastric carcinoma.

Previous reports have shown that the biochemical activity of heparanase is significantly correlated with the invasion and metastasis of malignant cells in vitro. Recently, it was found that the human heparanase gene was cloned and highly expressed in malignant cell lines and human solid malignant tumors. In the present study, we investigated the heparanase mRNA expression by using in situ hybridization in 116 paraffin-embedded tissues of primary gastric carcinomas. To explore its clinicopathologic significance, it was detected in the various steps of tumor progression and then compared with prognostic indicators. As a result, the heparanase expression was more prevalent in late-stage rather than early-stage carcinomas (P < .0001) and was more frequent in tumors of large size (P = .0212). Expression also correlated with lymphatic (P = .0086) and venous (P = .0171) invasion and with negative prognostic factors such as lymph nodal (P < .0001) and distant (P = .0221) metastases. However, in a multivariate analysis, messenger RNA expression of heparanase was not an independent prognostic factor. It was concluded that heparanase might play an important role in the development of invasion and metastasis of the gastric cancer. It was indicated that patients with heparanase-positive gastric carcinoma would have a greater chance of metastasis with a poor prognosis.

VEGF-D expression and lymph vessels play an important role for lymph node metastasis in papillary thyroid carcinoma

Papillary thyroid carcinoma frequently metastasizes to regional lymph nodes, and lymph node metastasis increases the risk of local regional relapse. Recent evidence suggests that vascular endothelial growth factor-D (VEGF-D) promotes lymphangiogenesis, which in turn promotes lymphatic metastasis. Therefore, the role of VEGF-D messenger RNA transcript levels and VEGF-D immunoreactivity in lymph node metastasis in papillary thyroid carcinoma was investigated. In addition, the role of blood vascular vessel, lymph vessel, and Flt-4-positive vessel densities were studied in relation to their suspected association with lymph node metastasis, and with VEGF-D expression. VEGF-D messenger RNA transcript levels by quantitative real-time reverse transcription-polymerase chain reaction and VEGF-D immunoreactivity by immunohistochemistry in 49 papillary thyroid carcinomas were also studied. This was followed by quantitative immunohistochemical staining for CD34, podoplanin, and Flt-4. Lymph node metastasis was significantly correlated with VEGF-D messenger RNA transcript levels (P=0.027) and VEGF-D immunoreactivity (P=0.019). Increased lymph vessel density was also correlated with VEGF-D expression and lymph node metastasis. In conclusion, our findings indicate that VEGF-D expression and increased lymph vessel density may have an important role for lymph node metastasis in papillary thyroid carcinoma.

p63 expression in normal, hyperplastic and malignant breast tissues.

Backgroundp63 is a homologue of the p53 tumor suppressor gene and its protein is selectively expressed in the basal cells of a variety of epithelial tissues. It has recently been confirmed that p63 is expressed in the basal cells of normal prostate glands but not in prostatic carcinomas. Whether expression of p63 in breast correlates with tumor progression is the focus of this study.MethodsForty cases, which all contained normal breast tissue, ductal hyperplasia, ductal carcinomain situ and invasive ductal carcinoma in the same patient were included in this investigation using an indirect immunohistochemical method and double staining.Resultsp63 was exclusively expressed in the myoepithelial cells of normal breast, partially expressed in ductal hyperplasia, rarely expressed in carcinomain situ and not expressed in invasive carcinomas.ConclusionsThe results suggest an association between loss of p63 expression and progression of breast ductal carcinoma. p63 immunostaining might be of assistance for distinguishing invasive ductal carcinoma from ductal carcinomain situ or rare questionable ductal hyperplastic lesions, leading to correct therapy clinically.

Metaplastic Carcinoma of the Breast: p53 Analysis Identified the Same Point Mutation in the Three Histologic Components

A rare case of metaplastic carcinoma of the breast with both squamous metaplasia and cartilaginous metaplasia was reported. Histologically, the neoplasm revealed complex features, which were consisting of invasive ductal carcinoma, squamous carcinomatous component and chondrosarcomatoid component. Gradual transition of each component was recognized microscopically. p53 mutation analysis disclosed the same point mutation in three histologically different components, but not in the normal epithelium. Based on the morphologic findings, immunohistochemical findings and the p53 mutation analysis, we concluded that these three components in the tumor originated from the same duct progenitor cells.

Expression of Bcl-2 but not Bax or p53 correlates with in vitro resistance to a series of anticancer drugs in breast carcinoma

Programmed cell death is an important determinant of the response to chemotherapy. Among the factors controlling this process, a significant role is played by bcl-2, bax and p53. The in vitro chemosensitivity of the 177 breast carcinomas was assessed by the histoculture drug response assay (HDRA) using mitomycin C (MMC), 5-fluorouracil (5-Fu), adriamycin (ADM), cisplatin (CDDP), and cyclophosphamide (CPA). The susceptibility of Bcl-2-negative tumors to all the drugs killing was significantly higher than that of Bcl-2-positive tumors. No relationship between Bax or p53 immunoreactivity and sensitivity for any of anticancer drugs studied was demonstrated. Immunohistochemical results regarding Bcl-2 are promising in the evaluation of the sensitivity of cancer cells to a series of anticancer drugs and might be therapeutically useful as an indicator of response to adjuvant chemotherapy for breast cancer.

Differentiation, proliferation and retinoid receptor status of papillary carcinoma of the thyroid

Messenger RNA expression of retinoic acid receptors (RARα, RARβ and RARγ) and retinoid X receptors (RXRα, RXRβ and RXRγ) was examined using reverse transcription‐polymerase chain reaction in 42 papillary thyroid carcinomas (PTCs). A loss of mRNA expression was observed in 18 cases of the 42 PTCs, including three cases for RARα, 14 cases for RARβ, six cases for RXRα and five cases for RXRβ. The expressions of RARγ and RXRγ were found in all 42 PTCs. Based on Ki 67/MIB1 labeling index (LI), the 42 PTCs were classified into Group A (20 cases; LI = 0–2%), Group B (17 cases; LI = 2–5%) and Group C (5 cases; LI > 5%). The PTCs of groups B and C showed solid, trabecular or scirrhous arrangements, infiltrative growth, loss of cellular polarity and cohesiveness more frequently, but capsulated growth pattern less frequently, when compared with PTCs of Group A. They also showed more frequent extrathyroidal extension than Group A. However, no significant differences were identified in sex, age, nodal status and tumor size. Loss of expression for one or more retinoid receptors frequently occurred in groups B and C. These results suggest that the loss of retinoid receptors might occur during the loss of differentiation and tumor progression of PTC.

Gastrointestinal stromal tumors: Clinicopathological study of Chinese cases

In the present study, we reviewed 73 Chinese cases of gastrointestinal stromal tumor (GIST), and analyzed factors in evaluating malignant potential, in particular focusing on Ki‐67 index and p53 expression to determine whether these can be used as prognostic indicators in GIST. The p53 positive rate was 50.7% and it was significantly higher in malignant (25/35; 71.43%) than in benign cases (13/38; 34.21%). A Ki‐67 labeling index of >10% was also significantly different between malignant (23/35; 65.71%) and benign cases (14/38; 36.84%). In the cases in which the patient died, 15/21 and 14/21 cases showed expression of p53 and Ki‐67, respectively; both had a higher expression than in surviving cases. Comparing the cases positive for both Ki‐67 and p53 with those positive for Ki‐67 or p53 alone, and those negative for both Ki‐67 and p53, the latter demonstrated the best prognosis. The study also indicated that the malignant potential of GIST is correlated with the mitotic index (≥1/10 high‐power fields; HPF), tumor size (≥5 cm), high cellularity, tumor invasive growth, tumor location, tumor hemorrhage and tumor necrosis.

Cytologic grading of invasive breast carcinoma : Correlation with clinicopathologic variables and predictive value of nodal metastasis

OBJECTIVE To estimate cytologic grade and correlate it with the other known prognostic factors, such as tumor differentiation, growth fraction, estrogen receptor status and nodal status. STUDY DESIGN Fine needle aspirates from 104 invasive ductal carcinomas were stained by the Papanicolaou method and examined for necrosis, cellular size, nuclear/cytoplasmic ratio, nuclear pleomorphism, nucleoli, chromatin granularity and density of chromatin. We established a semiquantitative scoring system based on the above features and correlated cytologic findings with clinicopathologic variables. RESULTS Histologic grade correlated positively with cytologic grade and negatively with estrogen receptor positivity. Moreover, high cytologic grade was associated with nodal metastasis and proliferative index labeling by MIB-1. CONCLUSION This study showed that our grading system for breast cancer on fine needle aspiration cytology is feasible on a routine diagnostic basis. Cytologic grading can provide more information than usual on tumor biologic behavior.

Parathyroid Gland Involvement by Papillary Carcinoma of the Thyroid Gland

OBJECTIVE To describe the phenomenon of parathyroid gland involvement by thyroid carcinoma and to explore its clinicopathologic significance. DESIGN We reviewed the clinicopathologic features and described the histopathologic characteristics of 20 cases of parathyroid involvement found in a series of 911 papillary thyroid carcinomas. RESULTS Parathyroid involvement occurred in 3 patterns: (1) direct invasion from the main tumor with an infiltrative growth, (2) invasion of the parathyroid gland with an expansive growth and formation of a pseudocapsule between the carcinoma and the parathyroid gland, and (3) metastatic deposition within the parathyroid gland itself. Among the 20 cases, 6 (30%) had primary tumors measuring 1 cm or less, and 14 (70%) had primary tumors measuring more than 1 cm. The cases with smaller primary tumors had a comparatively lower rate of nodal metastasis (50% vs 100%, P =.02). Furthermore, none of the cases with smaller primary tumors had invasion of extrathyroid structures other than parathyroid gland, but such invasion was common among the cases with larger primary tumors (0% vs 71%, P =.01). CONCLUSION To the best of our knowledge, this is the first report showing that parathyroid involvement occurs in papillary thyroid carcinomas even in the early stage of the disease.

Loss of cell cohesion in breast cytology as a characteristic of neuroendocrine carcinoma.

OBJECTIVE To characterize a specific group of breast cancers displaying a scattered single cell pattern in cytology and correlate it with histologic and immunohistochemical findings. STUDY DESIGN Of 135 consecutive malignant breast cytologic specimens, 12 cases were selected for their scattered single cell pattern on aspiration cytology. Immunohistochemical staining for neuroendocrine markers and prognostic parameters was performed on paraffin sections of corresponding primary breast carcinomas. RESULTS In the smears of the 12 cases, highly cellular neoplastic cells with a single cell pattern were observed predominantly. The tumor cells had relatively wide, granular cytoplasm and a low to moderate nuclear/cytoplasmic ratio. Histologically, they were arranged mainly in relatively large, solid nests and occasionally contained a tubular pattern with small amounts of stromal tissue. Five of the 12 cases demonstrated neuroendocrine differentiation with a positive immunoreaction for chromogranin A and synaptophysin. Except for the small mean size of the tumors (P < .01), no significant differences were identified among the prognostic parameters, including a nodal status, estrogen receptor status, growth fraction by Ki-67 or immunoreactivity for c-erbB-2, as compared with the other 123 cases. CONCLUSION Loss of cell cohesion in breast cytology is a good morphologic marker for identifying neuroendocrine breast carcinoma.