Down-regulation of Inositol Polyphosphate 4-Phosphatase Type II Expression in Colorectal Carcinoma

Sung, Ji Youn; Na, Kiyong; Kim, Hyun Soo

doi:10.21873/anticanres.11984

Cited by 9 publications

(11 citation statements)

References 33 publications

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“…Although the splice-site mutations of TP53 are very scarce in UEA and their effects have not been well characterized, the possibility that the novel splice-site mutation in this study is involved in the pathogenesis of UEA cannot be excluded. In addition, tuboovarian high-grade carcinoma with TP53 splice-site mutations (c.920-6_922delTCCTAGCAC and c.920-2delA) was found to exhibit wild-type expression patterns in the p53 immunostaining results (18). This study showed patchy and weak p53 expression in two cases of UEA with TP53 splicesite mutations.…”

Section: Discussionmentioning

confidence: 57%

“…Immunohistochemical staining. Immunostaining was performed using an automatic instrument [Ventana Benchmark XT (Ventana Medical Systems, Oro Valley, AZ, USA)] (10)(11)(12)(13)(14)(15)(16)(17)(18). Antigen retrieval was performed using the Cell Conditioning Solution (CC1, Ventana Medical Systems).…”

Section: Methodsmentioning

confidence: 99%

“…Negative controls were prepared by substituting the non-immune serum for primary antibodies, which resulted in no detectable staining. The p53 immunostaining patterns were interpreted as either missense mutation, nonsense mutation, or wild-type patterns when p53 expression was diffused and strong (>60% of tumor cell nuclei), completely absent (0%), or focal and weakly positive, respectively (11,14,16,18,19). The p16 immunostaining pattern was interpreted as block-positive when p16 expression was strong and horizontally continuous, and included nuclear or nuclear-pluscytoplasmic staining.…”

Section: Methodsmentioning

confidence: 99%

“…We performed a polymerase chain reaction (PCR)based microarray for HPV genotyping, using a commercially available HPV 9G DNA chip (BMT HPV 9G DNA Chip, Biometrix Technology, Chuncheon, Republic of Korea) (20)(21)(22). The 9G test examined the presence of 14 high-risk (16,18,31,33,35,39,45,51,52,56,58,59, 66, 68) and 5 low-risk (6,11,34,40,42) HPV types. The PCR mixture consisted of 10 μl of the extracted target DNA, 10 μl of the primer set (provided by the manufacturer), and a PCR premix (provided by the manufacturer), which contained dNTP and Taq DNA polymerase in an amplification buffer.…”

Section: Methodsmentioning

confidence: 99%

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Clinicopathological and Molecular Differences Between Gastric-type Mucinous Carcinoma and Usual-type Endocervical Adenocarcinoma of the Uterine Cervix

Jung

Bae

Kim

et al. 2020

Cancer Genomics Proteomics

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Background/Aim: We investigated differences in the clinicopathological and molecular characteristics between gastric-type mucinous carcinoma (GMC) and usualtype endocervical adenocarcinoma (UEA). Patients and Methods: We collected the clinicopathological information and performed targeted genomic sequencing analysis. Results: GMCs exhibited significantly deeper invasion depth, larger horizontal spread, more advanced stage, more frequent distant metastasis, and more frequent parametrial and vaginal extension. Disease-free survival time of GMC patients was significantly shorter than that of UEA patients. GMCs displayed mutant p53 immunostaining pattern, whereas UEAs exhibited p16 block positivity. GMCs harbored mutations in KRAS, TP53, NF1, CDKN2A, STK11, and ARID1A. One GMC exhibited MDM2 amplification. In contrast, UEAs harbored mutations in HRAS, PIK3CA, and BRCA2. Two UEAs were found to have novel TP53 mutations. Conclusion: GMC is associated with more aggressive behavior than UEA. Distinctive p53 and p16 immunostaining patterns enable differential diagnosis. GMC and UEA exhibit genetic heterogeneity with potentially actionable molecular alterations. Cervical cancer is the fourth most common gynecological malignancy and the fourth leading cause of cancer-related death in women worldwide (1, 2), although cervicovaginal cytology screening decreased the incidence rate of cervical cancer and its associated mortality rate. Adenocarcinoma of the uterine cervix is relatively less common than squamous cell carcinoma and accounts for approximately 10-20% of all cervical cancers (3, 4). However, despite the declined incidence of cervical cancer, the proportion of endocervical adenocarcinoma has increased (4-6). The International Endocervical Adenocarcinoma Criteria and Classification (IECC) is a recent system to classify endocervical adenocarcinoma into human papillomavirus (HPV)-associated adenocarcinoma (HPVA) and non-HPV-associated adenocarcinoma (NHPVA) categories based on morphological features (7). Identification of high-risk HPV, notable mitotic activity, and numerous apoptotic bodies across the glandular lumina allowed diagnosing HPVAs. The HPVAs were further divided into usual type, mucinous type (intestinal type, signet ring cell type, and not otherwise specified), villoglandular type, and invasive stratified mucin-producing carcinoma (invasive stratified mucin-producing intraepithelial lesion), depending on their cytoplasmic mucin component and nuclear characteristics. Meanwhile, NHPVAs include gastric-type mucinous carcinoma (GMC), mesonephric carcinoma, serous carcinoma, clear cell carcinoma, and endometrioid adenocarcinoma. Among these carcinomas, GMC, which is the second most common subtype of endocervical adenocarcinoma, is included in the 2014 World Health Organization (WHO) Classification of Tumours of Female Reproductive Organs (1). Although the incidence of 627 This article is freely accessible online.

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Section: Discussionmentioning

confidence: 57%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Clinicopathological and Molecular Differences Between Gastric-type Mucinous Carcinoma and Usual-type Endocervical Adenocarcinoma of the Uterine Cervix

Jung

Bae

Kim

et al. 2020

Cancer Genomics Proteomics

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“…The 4 µm-thick, FFPE slices were de-paraffinized and rehydrated using a xylene and alcohol solution. Immunostaining was performed using automated instruments (Ventana Benchmark XT (Ventana Medical Systems) and or Dako Omnis (Dako, Carpinteria, CA, USA)) [1,[18][19][20][21][22][23][24][25][26]. After antigen retrieval, the slices were incubated with primary antibodies including pan-cytokeratin (pan-CK; 1:600, clone AE1/AE3, Dako), CK7 (Dako, 1:100, clone OV-TL 12/30, Dako), CK20 (1:100, clone Ks20.8, Dako), caudal type homeobox 2 (CDX2; 1:400, clone EPR2764Y, Cell Marque, Rocklin, CA, USA), paired box 8 (PAX8; 1:50, polyclonal, Cell Marque), estrogen receptor (ER; 1:150, clone 6F11, Novocastra, Leica Biosystems, Newcastle Upon Tyne, UK), progesterone receptor (PR; 1:100, clone 16, Novocastra), p53 (1:300, clone DO-7, Novocastra), p16 (prediluted, clone E6H4, Ventana Medical Systems), p63 (1:50, clone 4A4, Dako), and GATA-binding protein 3 (GATA3; 1:150, clone L50-823, Cell Marque).…”

Section: Immunohistochemistrymentioning

confidence: 99%

Endometrium-Limited Metastasis of Extragenital Malignancies: A Challenge in the Diagnosis of Endometrial Curettage Specimens

Choi

Joo

et al. 2020

Diagnostics

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Malignancies of extragenital origin very rarely metastasize to the uterine body. Endometrium-limited metastases may pose diagnostic challenges in endometrial curettage specimens as they may be misdiagnosed as primary endometrial tumors. We investigated the clinicopathological characteristics of seven cases with endometrial-limited metastases from carcinomas of the nasopharynx (n = 1), breast (n = 2), colon (n = 2), stomach (n = 1), and appendix (n = 1). The patients’ ages ranged from 36 to 71 (mean: 55.4) years. None of the patients had a remarkable gynecological history, and the presenting sign in all cases was abnormal uterine bleeding. Although myometrial involvement was absent, multiple metastases were already present in extrauterine locations such as the lung, liver, bone, abdominopelvic peritoneum, and omentum. All patients underwent ultrasonographic examination prior to endometrial curettage. The histologies of the endometrial metastases identified from the curettage specimens were identical to those of the corresponding primary tumors. Ancillary tests including immunostaining and Epstein–Barr virus-encoded RNA in situ hybridization confirmed the extragenital origin. Endometrium-limited metastases from extragenital malignancies are extremely rare. They present with abnormal vaginal bleeding and mimic endometrial carcinomas of endometrioid or poorly differentiated types. Since their clinical presentations and histological features are similar to those of primary endometrial tumors, pathologists should consider the possibility of metastases while evaluating endometrial curettage specimens obtained from patients with a history of extragenital malignancies.

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Expression and functional characterization of INPP4B in gallbladder cancer patients and gallbladder cancer cells

Meng

et al. 2021

BMC Cancer

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Background Inositol polyphosphate 4-phosphatase type II (INPP4B) is a negative regulator of the PI3K-Akt signalling pathway and plays a contradictory role in different types of cancers. However, the its biological role played by INPP4B in human gallbladder cancer (GBC) has not been elucidated. In this study, we investigated the expression, clinical significance and biological function of INPP4B in GBC patients and cell lines. Methods The INPP4B protein expression levels in gallbladder cancer tissues and normal gallbladder tissues were detected by immunohistochemistry, and the clinical significance of INPP4B was analysed. Knockdown and overexpression of INPP4B in GBC-SD and SGC-996 cells followed by cell proliferation, clonogenic, apoptosis detection, scratch wound-healing and transwell assays were used to identify INPP4B function in vitro. Results INPP4B was up-regulated in human GBC tissues compared with normal gallbladder tissues and was related to histopathological differentiation (p = 0.026). Here, we observed that INPP4B was highly expressed in high-moderately differentiated tumours compared with low-undifferentiated tumours (p = 0.022). Additionally, we found that INPP4B expression was not associated with overall survival of GBC patients (p = 0.071) and was not an independent prognostic factor. Furthermore, when we stratified the relationship between INPP4B expression and the prognosis of GBC based on histopathological differentiation, we found that INPP4B played a contradictory role in GBC progression depending on the degree of differentiation. In addition, INPP4B knockdown inhibited the proliferation, colony formation, migration and invasion in GBC cells, while INPP4B overexpression had the opposite effects in vitro, which indicates its role as an oncoprotein. Conclusions These findings suggested that INPP4B may play a dual role in the prognosis of GBC depending on the degree of differentiation and that INPP4B might act as an oncogene in gallbladder cancer cells.

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Down-regulation of Inositol Polyphosphate 4-Phosphatase Type II Expression in Colorectal Carcinoma

Abstract: Our results indicate that INPP4B is down-regulated in CRC and that INPP4B is involved in the development and progression of CRC.

Cited by 9 publications

References 33 publications

Clinicopathological and Molecular Differences Between Gastric-type Mucinous Carcinoma and Usual-type Endocervical Adenocarcinoma of the Uterine Cervix

Clinicopathological and Molecular Differences Between Gastric-type Mucinous Carcinoma and Usual-type Endocervical Adenocarcinoma of the Uterine Cervix

Endometrium-Limited Metastasis of Extragenital Malignancies: A Challenge in the Diagnosis of Endometrial Curettage Specimens

Expression and functional characterization of INPP4B in gallbladder cancer patients and gallbladder cancer cells

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