Molecular Testing for Gastrointestinal Cancer

With recent advances in molecular diagnostic methods and targeted cancer therapies, several molecular tests have been recommended for gastric cancer (GC) and colorectal cancer (CRC). Microsatellite instability analysis of gastrointestinal cancers is performed to screen for Lynch syndrome, predict favorable prognosis, and screen patients for immunotherapy. The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor has been approved in metastatic CRCs with wildtype RAS (KRAS and NRAS exon 2–4). A BRAF mutation is required for predicting poor prognosis. Additionally, amplification of human epidermal growth factor receptor 2 (HER2) and MET is also associated with resistance to EGFR inhibitor in metastatic CRC patients. The BRAF V600E mutation is found in sporadic microsatellite unstable CRCs, and thus is helpful for ruling out Lynch syndrome. In addition, the KRAS mutation is a prognostic biomarker and the PIK3CA mutation is a molecular biomarker predicting response to phosphoinositide 3-kinase/AKT/mammalian target of rapamycin inhibitors and response to aspirin therapy in CRC patients. Additionally, HER2 testing should be performed in all recurrent or metastatic GCs. If the results of HER2 immunohistochemistry are equivocal, HER2 silver or fluorescence in situ hybridization testing are essential for confirmative determination of HER2 status. Epstein-Barr virus–positive GCs have distinct characteristics, including heavy lymphoid stroma, hypermethylation phenotype, and high expression of immune modulators. Recent advances in next-generation sequencing technologies enable us to examine various genetic alterations using a single test. Pathologists play a crucial role in ensuring reliable molecular testing and they should also take an integral role between molecular laboratories and clinicians.

A Rare Case of an Epidermal Inclusion Cyst in the Joint Capsule of the Thumb

No abstract available.

Histological Changes in Levator Aponeurosis According to Blepharoptosis and Aging

BACKGROUND: Many studies about the levator aponeurosis complex of the blepharoptosis have already been presented. However, the studies about the changes of the levator aponeurosis are relatively insufficient. So, this study was performed to observe histological changes of levator aponeurosis that arise depending on the severity of blepharoptosis and the age. METHODS: Twenty patients who have undergone surgical treatment for blepharoptosis from 2013 to 2014 were analyzed in this study. Patients were categorized mild or severe group according to the severity of blepharoptosis, and the age. Through the blepharoplasty incision, we harvested the specimens of the levator aponeurosis on the upper border of tarsal plate. After staining the specimens with the Verhoeff-van Gieson technique, the changes of elastin was analyzed in a histopathological manner. RESULTS: Light microscopy of the levator aponeurosis stained positively for elastic fibers using the Verhoeff-van Gieson technique. Elastic fibers appear to have direct connections with the collagen fiber of the levator aponeurosis. The amount of the elastin was decreased in the old age group. And the amount of elastin was decreased markedly in severe blepharoptosis group. CONCLUSIONS: The elastin of the levator aponeurosis was decreased in old age and elastin tended to decreased markedly in severe levator function group. The levator aponeurosis plays a greater role in the eyelid ptosis. Therefore, knowledge about the histologic changes of the levator aponeurosis may give more help us to understand the high recurrence rate of the blepharoptosis in old age. Also, considering this information, will be helpful to the blepharoptosis surgery.

Transglutaminase 2 Expression and Its Prognostic Significance in Clear Cell Renal Cell Carcinoma

BACKGROUND: A few recent studies have demonstrated a possible role of transglutaminase 2 (TG2) in tumorigenesis or progression of renal cell carcinoma (RCC). The aim of this study was to examine TG2 expression and its clinicopathologic significance in a large number of human clear cell RCCs (CCRCCs). METHODS: We analyzed 638 CCRCC patients who underwent partial or radical nephrectomy between 1995 and 2005. The expression of TG2 was determined by immunohistochemistry and categorized into four groups, according to staining intensity: negative (0), mild (1+), moderate (2+), and strong (3+). RESULTS: TG2 staining intensity was negative in 8.5% of CCRCC (n=54), 1+ in 32.6% (n=208), 2+ in 50.5% (n=322), and 3+ in 8.5% (n=54). Strong TG2 expression was correlated with high Fuhrman nuclear grade (p=.011), high T category (p=.049), metastasis (p=.043) and male sex (p<.001) but not with N category.The survival analysis showed a significant association between strong TG2 expression and worse overall and cancer-specific survival (p=.027 and p=.010, respectively). On multivariate analysis, strong TG2 expression was a marginally significant prognostic indicator for Fuhrman nuclear grade and TNM staging (p=.054). CONCLUSIONS: Our study is the first to demonstrate the clinicopathologic significance of TG2 expression in a large number of human CCRCC samples. Strong TG2 expression was associated with high nuclear grade and poor prognosis.

Distribution of Human Papillomavirus 52 and 58 Genotypes, and Their Expression of p16 and p53 in Cervical Neoplasia

BACKGROUND: This study investigates the prevalence of human papillomavirus (HPV) 52 and 58 genotypes among women residing in Busan, and the expression of p16 and p53 proteins in cervical neoplasia with HPV 52 and 58 infections. METHODS: A total of three hundred fifteen cases were analyzed using the HPV DNA chip test for HPV genotypes, and of these, we retrospectively examined p16 and p53 expression in 62 cases of cervical tissues infected with HPV 52 and 58 using immunohistochemistry. RESULTS: HPV 52 and 58 genotypes were identified in 62 (54.9%) out of 113 high-risk, HPV-infected cases. Of the cases examined, there were 19 single HPV 52 infections (16.8%), 23 single HPV 58 infections (20.4%), 4 multiple HPV 52 infections (3.5%), and 16 multiple HPV-58 infections (14.2%). Immunoreactivity of p16 and p53 was observed in 41 (66.1%) and 23 (37.1%) of the 62 cases of cervical neoplasia infected with HPV 52 and 58 genotypes, respectively. CONCLUSIONS: This study demonstrates a high prevalence of HPV 52 and 58 genotypes, in addition to HPV 16, among high-risk strains of cervical neoplasia in Korea. These findings suggest that development of more vaccines would be beneficial for the prevention of the various HPV genotypes.

Effect of Botulinum Toxin Type A on a Rat Surgical Wound Model

\ OBJECTIVES: The tension on a wound is one of the important factors that determine the degree of fibrosis and scar formation. We hypothesized that local botulinum toxin type A (Botox) induced paralysis of the musculature subjacent to a surgical wound with a skin defect would minimize the repetitive tensile forces on the surgical wound's edges, and this will result in a decreased fibroplastic response and fibrosis of the wound. METHODS: This is a prospective randomized experimental study. Two distinct surgical wounds were made to the dorsum of 15 adult rats, respectively. One of the 2 wounds was injected with Botox, and the other wound was used as a control, and this was done for all the rats' wounds. We evaluated the wound size, the degree of fibrosis and inflammation, the blood vessel proliferation, the thickness of the wound and the expression of transforming growth factor (TGF)-beta1 in the wounds. RESULTS: There were significant differences of wound size at the 3rd and 4th week between the Botox and control groups (P<0.05). The Botox group showed less infiltration of inflammatory cells than the control group at the 2nd week (P<0.05). The Botox group showed a smaller number of fibroblasts and less fibrosis than the control group at the 4th week (P<0.05). The Botox group showed much strong collagen density than the control group at the 8th week (P<0.05). For the immunohistochemical staining, there was a lower transforming growth factor (TGF)-beta1 expression in the Botox group than that of the control group at the 4th week (P<0.05). CONCLUSION: The wounds of the Botox-treated group showed a larger wound size, less infiltration of inflammatory cells and less fibrosis, a much greater amount of collagen and a lower expression of TGF-beta1 than did the control group. Botox might be used to decrease the fibrosis of a surgical wound without damaging the epithelial growth in situations for which decreased fibrosis is necessary, such as for treating laryngeal, tracheal and nasal stenosis.

Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) Syndrome Induced by Celecoxib and Anti-tuberculosis Drugs

Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome reflects a serious hypersensitivity reaction to drugs, characterized by skin rash, fever, lymph node enlargement, and internal organ involvement. So far, numerous drugs such as sulfonamides, phenobarbital, sulfasalazine, carbamazepine, and phenytoin have been reported to cause the DRESS syndrome. We report a case in a 29-yr-old female patient who had been on celecoxib and anti-tuberculosis drugs for one month to treat knee joint pain and pulmonary tuberculosis. Our patient's clinical manifestations included fever, lymphadenopathy, rash, hypereosinophilia, and visceral involvement (hepatitis and pneumonitis). During the corticosteroid administration for DRESS syndrome, swallowing difficulty with profound muscle weakness had developed. Our patient was diagnosed as DRESS syndrome with eosinophilic polymyositis by a histopathologic study. After complete resolution of all symptoms, patch tests were positive for both celecoxib and ethambutol. Although further investigations might be needed to confirm the causality, celecoxib and ethambutol can be added to the list of drugs as having the possibility of DRESS syndrome.

The Expression of Thymidine Phosphorylase in Cancer-infiltrating Inflammatory Cells in Stomach Cancer

Thymidine phosphorylase (TP) has shown to be up-regulated in several cancers and to play a role in angiogenesis and invasion. Most studies regarding TP have focused on cancer cells. Recently, evidences suggest that TP in cancer-infiltrating inflammatory cells (CIICs) also affect the cancer cell behavior. To evaluate the significance of TP expression of CIICs in gastric cancer, we assessed TP expression of cancer cells and CIICs separately using immunohistochemical assay on 116 paraffin-embedded tissue samples from stomach cancer patients and investigated their clinical significance. When subjects were divided into 4 groups according to the TP expression: cancer/matrix (+/+), C/M (+/-), C/M (-/+), and C/M (-/-), intratumoral microvessel density scores were higher in the C/M (+/-) group than in the C/M (-/-) group (p=0.02). For lymph node metastasis and survival, there were no significant differences among the 4 groups. However, there were significant differences in survival (p=0.035) and LN metastasis (p=0.023) between the two groups divided by TP expression of CIICs alone irrespective of TP expression of cancer cells. Taken together, this study suggested the TP expression in CIICs could affect lymph node metastasis and patients' survival in gastric cancer.

A Case of an Untreated Acute Myeloid Leukemia Patient with Invasive Aspergillosis that Developed at the Colon / 대한혈액학회지

Invasive aspergillosis needs to be paid extra attention to these day since chemotherapy and stem cell transplantation bring about immune suppression. The lung is the main portal of entry and once involved, invasive aspergillosis may be delivered by hematogenous spread into the central nervous system, liver, spleen, gut and adrenal gland. However infections through the gastrointestinal track are not common. In these cases, abdominal pain and diarrhea can be the major symptoms and amphotericin B is the treatment of choice. We report here on a patient with untreated acute myeloid leukemia who suffered from bloody diarrhea without any lung lesion; this patient had ulcer close to cecum on colonoscopy, and then he was diagnosed as suffering with aspergillosis with H&E staining and PAS staining on the biopsy specimen.

Alteration of G1/S Cell Cycle Regulatory Proteins in Ovarian Epithelial Tumors

BACKGROUND: Disturbances of the cell cycle regulatory proteins are key events underlying the development and/or progression of human malignancies. The aim of this study was to evaluate the expression of G1/S cell cycle regulatory proteins in ovarian epithelial tumor. METHODS: We simultaneously evaluated the expression of cyclin D1, cyclin E, CDK4, CDK2, p16, Rb, E2F1, p53 and the Ki67 labelling index (LI) by immunohistochemical methods in 148 cases of ovarian epithelial tumor of the benign (n=47), borderline (n=29), and malignant type (n=72). RESULTS: The expression of cyclin E, CDK2, p16, Rb, E2F1, p53 and the Ki67 LI gradually increased from the benign type, through the borderline type, to the malignant tumors. Between the borderline and malignant tumors, the increased expression of cyclin E, E2F1, and p53, and the decreased expression of Rb were significantly associated with malignancy. The reduced Rb expression and the increased E2F1 expression were correlated with the FIGO stage and the histologic grade in the malignant ovarian epithelial tumors. CONCLUSIONS: Cyclin E, E2F1, and p53 overexpressions and the loss of Rb are the important components during carcinogenesis of ovarian epithelial tumors. Our results suggest that in- creased expression of E2F1 should be considered as a new parameter for the prognosis of patients with malignant ovarian epithelial tumors.

Assessment of Apoptosis by M30 Immunoreactivity and the Relationship with the MSI status and the Clinicopathological Characteristics of Colorectal Carcinomas

BACKGROUND: The monoclonal antibody M30 recognizes a neoepitope of cytokeratin 18 that's produced during the process of apoptosis, and it is reactive in formalin-fixed, paraffin-embedded tissue. The detailed nature of apoptosis in colorectal cancer is unclear, especially in regard to the MSI status and the clinicopathologic factors. The purpose of this study was to elucidate the apoptosis assessed by M30 immunoreactivity in colorectal cancer and its relationship with the MSI status and the various clinicopathologic factors of colorectal cancers. METHODS: 101 colorectal cancers were classified according to levels of MSI as 12 MSI-H, 4 MSI-L and 85 MSS. Apoptosis was quantified by immunohistochemistry with using M30 CytoDEATH anti-body. RESULTS: The apoptotic index assessed by M30 was significantly increased in the MSI-H and MSI-L colorectal cancer compared to that in the MSS colorectal cancer. Right sided colon cancer showed a significant higher apoptotic index than did the left sided colon cancer. There was also a tendency for decreased apoptosis in metastatic colorectal cancers (Duke's stage D). There was somewhat of an increase of apoptosis in colorectal cancers with mucinous carcinoma and medullary carcinoma, and also in the colorectal cancers with an increased TIL count, but this was not statistically significant. CONCLUSION: M30 immunoreactivity is a valuable method to detect apoptosis in formalin-fixed, paraffin-embedded tissue and it might explain that MSI-H colorectal cancer shows better clinical behavior than MSS colorectal cancer in regard to the increased apoptosis.

MTA1 expression in epithelial ovarian neoplasm / 대한산부인과학회지

OBJECTIVE: MTA1 has been identified as a metastasis-promiting gene, and its gene expression is correlated with invasion and metastasis in several cancers. We examined MTA1 expression levels in epithelial ovarian neoplasm. METHODS: Expression of MTA1 was evaluated by immunohistochemistry and tissue array in 53 benign tumors, 27 borderline tumors and 68 malignant tumors. The data was analyzed in reference to various clinicopathological parameters. RESULTS: Increased expression of MTA1 was significantly correlated with histologic grade and FIGO stage. There was no relationship between MTA1 expression and age, histologic type, tumor size. CONCLUSION: These results suggest that MTA1 is closely related to invasiveness and progression in epithelial ovarian neoplasm. The MTA1 could thus potentially provide information on the mechanism of cancer invasion and metastasis.

Thymidine phosphrylase (TP) in cancer-infiltrating inflammatory cells in stomach cancer: the significance of TP in prognosis and tumor angiogenesis / 대한내과학회지

BACKGROUND: Thymidine phosphorylase (TP) is an enzyme catalyzing the reversible phosphorolysis of thymidine to thymine and 2-deoxyribose-1-phosphate. TP plays a role in angiogenesis. Evidences suggest that infiltrating inflammatory cells adjacent cancer cells may affect tumor cell behavior. To evaluate each of these significances of TP expression in cancer cell and cancer-infiltrating inflammatory cells, we investigated TP expression patterns in cancer cells and infiltrating inflammatory cells adjacent cancer cells separately and the relationship between TP expression and angiogenesis or survival. METHODS: Immunohistochemistry assays were performed with anti-TP monoclonal antibody (Roche Japan) and anti-factor VIII polyclonal antibody (Dako) on 92 paraffin-embedded tissue samples from stomach cancer patients. A single pathologist scored the slides for percent positivity of tumor cells, intensity, localization and distribution of expression. TP reactivity in tumor cells (cancer) and infiltrating mononuclear cells adjacent cancer cells (matrix) was separately accessed. According to the pattern of TP expression, subjects were divided into 4 groups for further analysis: cancer(C;+)/matrix(M;+), cancer(+)/matrix(-), cancer(-)/matrix(+) and cancer(-)/matrix(-). With these 4 subsets of TP expression patterns, we evaluated cancer cell differentiation, intratumoral microvessel density, extent of tumor invasion, LN stage, and patient survival to find any differences among the subsets. RESULTS: Of 92 stomach cancer tissue, C/M(+/+), C/M(+/-), C/M(-/+), and C/M(-/-) were observed in 33patients, 19, 30, and 10, respectively. Microvessel density scores were higher in cancer(+)/matrix(-) group compared in cancer(-)/matrix(-) group (p=0.02). Of 4 TP expression subsets, other clinical factors such as histology, extent of tumor invasion, and LN metastasis were not associated with TP expression. CONCLUSION: This study suggested the TP in cancer-infiltrating inflammatory cell as well as cancer cells themselves may play an important role in angiogenesis as co-active factors in stomach cancer.

A Phase II Trial of Haptaplatin/5-FU and Leucovorin for Advanced Stomach Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Heptaplatin (SKI-2053 R) is a new platinum analogue, with a better toxicity profile than cisplatin, and has antitumor activity even in cisplatin resistant cell lines. 5-fluoruracil (5-FU) has shown synergy with platinum compounds. This phase II trial was designed to determine the efficacy and toxicities of heptaplatin/ 5-FU (5-fluorouracil) for treating stomach cancer. MATERIALS AND METHODS: Thirty-two patients with advanced, measurable gastric adenocarcinomas were enrolled in this trial. The treatment consisted of heptaplatin, 400 mg/m2/day (1 hour IV infusion), on day 1 and 5-FU, 800 mg/m2/day (12 hours IV infusion), on days 1 to 5. The cycles were repeated every 3 weeks. RESULTS: Of the 26 evaluable patients, 9 had partial responses and 1a complete response (overall response rate, 38%; 95% confidence interval, 19~57%). The median response duration was 23 weeks (range: 4~60 weeks). The median time to progression was 26 weeks (range: 3~68 weeks). The grades III-IV toxicities were mostly hematological toxicities: leucopenia was observed in 11 patients (35%) and thrombocytopenia 4 (13%). No definite neuropathy was observed. Grade I-II nephropathy was also noted: grade I high BUN/creatinine levels occurred in 5 patients (16%), grade II proteinuria 2 (6%), grade I proteinuria 5 (16%). Neutropenic fever developed in 5 patients (16%) and 1 died of pneumonia in a neutropenic state. CONCLUSION: This study suggests that the regimen of Heptaplatin/5-FU should be effective and have a favorable toxicity profile for the patients suffering with advanced stomach cancer.

Altered Expression of DNA Topoisomerase IIalpha, Ki-67, p53 and p27 in Non-Hodgkin's Lymphoma

BACKGROUND: Topoisomerase II (TOPO II) is an enzyme that separates intertwined chromosomes during DNA synthesis by transiently breaking and joining DNA strands. The level of TOP II is one of the determinants of cellular sensitivity to anti-tumor drugs in non-Hodgkin's lymphoma patients. The alpha form of TOPO II has been recently used as a marker of cellular proliferation. High levels of TOPO IIalpha are expressed in aggressive and proliferative tumors. METHODS: This study was designed to evaluate the relationship between TOPO IIalpha expression and clinicopathological parameters including age, gender, the serum LDH level, the serum beta2-microglobulin level and stage, or expressions, of Ki-67, p53 and p27, in non-Hodgkin's lymphoma. We analyzed forty-one biopsied tissue specimens from patients with non-Hodgkin's lymphoma. RESULTS: The expression of TOPO IIalpha increased with the clinical stage and it was correlated with Ki-67 and p53 expressions. However, TOPO IIalpha expression did not have any significant correlation with age, gender, the serum LDH level, the serum 2-microglobulin level and the p27 expression. CONCLUSIONS: TOPO IIalpha expression is a useful marker of cellular proliferation and it may serve as a prognostic factor of a tumor's progression and aggressiveness in non-Hodgkin's lymphomas.

Immunocytochemical Staining for p16 of Atypical Squamous Cells in Cervicovaginal Smear / 대한세포병리학회지

It was reported that the main cause of intraepithelial neoplasm and squamous cell carcinoma of the uterine cervix is human papilloma virus infection, and that the expression of p16 is increased in cells infected by human papilloma virus. We performed an immunocytochemical staining for protein p16 in 17 cases of cervocovaginal smears initially diagnosed as atypical squamous cells of undetermined significance, to know whether the staining could help the differentiation of neoplastic cells from reactive atypical cells. Of 17 smears, 6 were diagnosed finally as high grade intraepithelial neoplasm or invasive squamous cell carcinoma by follow-up biopsy and smear, and 5 of the 6 were positive for p16. Three were diagnosed as koilocytosis, and one of them was weakly positive for p16. Eight were diagnosed as reactive atypical cells, and all of them were negative for p16. We thought that immunocytochemical staining of p16 in cervocovaginal smears could help the differentiation of neoplastic cells from reactive atypical cells.

A Case of Early Developed Secondary Renal Amyloidosis in a Patient with Rheumatoid Arthritis (RA) / 대한신장학회잡지

We experienced a case of secondary renal amyloidosis diagnosed by renal biopsy in a patient who had been diagnosed as RA two years ago. A 62-year old man was admitted to neurology departement because of right hemiplegia. During conservative care at neurology department, he was consulted to us because of aggravated generalized edema and proteinuria. He was diagnosed as rheumatoid arthritis and ulcerative colitis two years ago, and then he had taken prednisolone, methotrexate, mesalazine regularly. At physical examination, there was no abnormal finding except pretibial pitting edema and right hemiplegia. In urinalysis, specific gravity was 1.025, pH was 5.5, protein was 4+ and RBC 0-1/ HPF and WBC 0-1/HPF. Total protein of 24 hour's urine was 5.5 g/day. The blood BUN and creatinine level were 16.4 mg/dL, 0.4 mg/dL and cholesterol level were 154 mg/dL, total protein and albumin were 4.4 g/dL and 1.9 g/dL. Serum RA factor and CRP showed high level as 94.90 IU/mL and 118.00 mg/L. On urine electrophoresis, albuminuria was dominant but M-spike was not founded. On urinalysis taken at the time of first diagnosis of rheumatoid arthritis two years ago, proteinuria was negative and serum albumin levels was 3.6 g/dL. At that time, there was no evidence of nephropathy. In renal biopsy, electron microscope showed heavy nonbranching amyloid fibrils accumulated in mesangium and polarized light microscopy after Congo-red staining revealed apple-green birefringent amyloid deposits in glomeruli and blood. So we diagnosed renal amyloidosis associated with RA.

Histology of Upper Pole Kidney in Patients with Ureterocele / 대한비뇨기과학회지

PURPOSE: The histological changes in the upper pole of excised duplex kidneys with ureterocele were reviewed and the histological variations with respect to age and ureterocele position were assessed. MATERIALS AND METHODS: During the last ten years, 10 patients with duplex system ureterocele underwent an upper pole nephrectomy. A total of 10 specimens, of which 4 and 6 were diagnosed at younger than 1 year old and older than 1 year old, and 5 each involving intravesical and ectopic locations, respectively, were available for independent review by a single pathologist. Histological lesions were classified into the 5 categories; chronic interstitial inflammation, interstitial fibrosis, tubular atrophy, glomerulosclerosis and dysplasia. Each category was divided into moderate/severe histological lesions (greater than 25% involvement) and minimal/mild lesions (25% or less involvement). RESULTS: Chronic interstitial inflammation, interstitial fibrosis, tubular atrophy, glomerulosclerosis and dysplasia in each of the specimens were graded as moderate/severe (greater than 25% involved) in 50, 50, 60, 10 and 80% of the subjects, respectively. The ureteroceles detected at an early stage were not associated with less severe upper pole histological lesions. Also, no pathological differences were observed when comparing specimens according to the ureteroceles positions. CONCLUSIONS: It appears that the histological lesions observed may not be progressive or reversible. Therefore, it is suggested that enhancement of the upper pole renal function seems unjustified in the light of the histological evidence, and the goals of clinical management should focus on preventing complications and secondary procedures.

Solitary Fibrous Tumor of the Urinary Bladder: A Case Report

Solitary fibrous tumor (SFT) most commonly affects the pleura and these tumors have been recently reported to be found in unusual locations. We describe here a solitary fibrous tumor of the urinary bladder that was removed from a 79-year-old man having a history of gross hematuria and dysuria. Transabdominal ultrasonography showed a huge soft tissue mass in the urinary bladder. The cut surface of the tumor showed a grayish-white, hemorrhagic and gelatinous appearance. Necrosis was not found. Microscopically, the tumor showed a proliferation of spindle or ovoid cells that were intervened by a collagenous stroma. A variety of growth patterns was identified but the so-called patternless pattern was the predominant one. The spindle cells had almost no mitotic figures, and there was very little or no nuclear atypia. Immunohistochemical stains showed a strong reactivity for CD34 and a focal reactivity for bcl-2. The ultrastructure of the tumor cells showed mesenchymal-myofibroblastic traits.

Studies on the Expression of the p16 (INK4A), p53, and Ki-67 Labeling Index in Inflammatory and Neoplastic Diseases of the Uterine Cervix

BACKGROUND: Prior studies of p16, p53, and Ki-67 expression have suggested that these markers may be preferentially expressed in cervical neoplasms. The purpose of this study was to assess the expression and clinical significance of p16, p53 proteins, and the Ki-67 labeling index in the cervical lesions. METHODS: We analyzed 54 uterine cervical specimens obtained by surgical biopsy. The expression of p16, p53 proteins, and Ki-67 was evaluated by immunohistochemical methods. The immunohistochemical findings were then correlated with the histologic diagnosis. RESULTS: Positive scores for p16, p53, and Ki-67 were seen in 75% (6/8), 0% (0/8), and 13% (1/8) of low grade intraepithelial lesions (LSIL), respectively, and 100% (23/23), 17% (4/23), and 74% (17/23) of high grade intraepithelial lesions (HSIL), respectively, and 100% (10/10), 20% (2/10), and 70% (7/10) of invasive squamous cell carcinomas, respectively. Both normal epithelium and inflammatory lesions scored negative for these three markers in all of the 13 cases. p16 and Ki-67 expression correlated with the severity of uterine cervix lesions. CONCLUSIONS: p16 and Ki-67 are complementary surrogate biomarkers for cervical squamous intraepithelial neoplasia. However, immunohistochemical expression for p53 has no correlation with the grade of cervical squamous intraepithelial neoplasia.