Villoglandular papillary adenocarcinoma of the uterine cervix with lymph node metastasis - A case report and review of the literature

Villoglandular papillary adenocarcinoma was first described by Young and Scully in 1989 as a distinct entity with the histological features of exophytic growth proliferation, villous and papillary architecture and mild to moderate nuclear atypia. We report one case of villoglandular papillary adenocarcinoma (VGPA) of the uterine cervix with lymph node metastasis and reviewed the clinicopathological features of six other cases reported in the literature. Our patient is the seventh similar reported cases. They ranged in age from 29 to 54 (mean, 41) years. Five had lymphovascular invasion. All except our patient were treated with radical hysterectomy and radiotherapy. She was followed-up for 7 months and unfortunately died due to chest infectio

Growing Teratoma Syndrome: A Rare Case Report and Review of the Literature

Growing teratoma syndrome is rare and usually it occurs in the younger aged group. The use of chemotherapy following initial surgical resection will yield the diagnosis following tumour enlargement. Complete resection is usually curative and renders better prognosis

The role of antenatal vitamin e supplementation in the prevention of neonatal jaundice.

Objective: To determine the effect of maternal antenatal vitamin E supplementation on neonatal jaundice. Methods: A randomized double blind controlled trial assessing the role of vitamin E in the prevention of preeclampsia was conducted in a tertiary hospital over two years. From 12-16 weeks gestation until delivery, primigravida mothers with singleton pregnancies received either 100 mg daily vitamin E in the form of tocotrienol rich fraction, or placebo. The newborns were assessed for jaundice. Results: Among 262 infants, 136 were in the vitamin E group and 126 in the placebo group. The incidence of neonatal jaundice was similar: 38% (54/136) in the vitamin E group and 36% (45/126) in the placebo group (p= 0.10). Nevertheless, the vitamin E group had a tendency for lower peak serum bilirubin, although not significantly so. Conclusion: Maternal antenatal vitamin E supplementation had no effect on the incidence of neonatal jaundice

Immunohistochemical study of p16INK4A and survivin expressions in cervical squamous neoplasm.

Introduction: Cervical cancer is the second most common cancer affecting Malaysian women. Despite the implementation of pap smear screening, many women are still diagnosed only in the advanced stage of cervical cancer. This could partly be due to failure of detection of its precursor lesions; hence the need to search for novel biomarkers to assist in the screening and diagnosis of cervical neoplasia. This study aims to determine the expression of p16 INK4A and survivin as possible predictive biomarkers in cervical squamous neoplasm. Material and Methods: This is a retrospective study on 201 cases of cervical neoplasm comprising of 129 cervical intraepithelial neoplasia (CIN) and 72 squamous cell carcinoma (SCC). All samples were evaluated by two independent observers using p16INK4A and survivin monoclonal antibodies. The p16INK4A expression was graded as negative, focal and diffuse positivity. The intensity for survivin expression was graded as weak, moderate and intense. Results: It is seen that p16INK4A expression in CIN 1, CIN 2 and CIN 3 were 25.4%, 42.9% and 95.9% respectively. Majority of SCC (98.6%) showed p16INK4A expression. Survivin expressions in CIN 1, CIN 2, CIN 3 and SCC were 56.7%, 33.4%, 87.5% and 98.6%. There was a linear relationship between increasing grade of CIN and p16INK4A expressions. Conclusion: Our study showed that p16INK4A expressions correlate well with the increasing grade of CIN. Although survivin does not correlate well to the increasing grade of CIN, it could be useful in differentiating CIN 3 from SCC

Utility of Ki-67 and p53 in distinguishing cervical intraepithelial neoplasia 3 from squamous cell carcinoma of the cervix

The differentiation between cervical intraepithelial neoplasia 3 (CIN 3) and early squamous cell carcinoma (SCC) of the cervix may be difficult in certain situations. Identification of invasion beyond the basement membrane is the gold standard for the diagnosis of the latter. The objective of this study was to determine whether the use of Ki-67 and p53 could help in solving the above dilemma. This was a retrospective study on 61 cases of cervical neoplasms comprising of 25 cases of CIN 3 and 36 SCC. All cases were evaluated by immunohistochemistry using Ki-67 and p53 monoclonal antibodies. Results showed that the differences of Ki-67 and p53 expression between CIN 3 and SCC were statistically significant. In conclusion, Ki-67 and p53 may serve as helpful adjuncts to routinely-stained histological sections in differentiating between CIN 3 and SCC

Expression of p16 and pKi-67 in cervical preneoplasia and neoplasia

This study was conducted to investigate the expression of p16 and pKi-67 in normal, preneoplasia and neoplasia lesions of the uterine cervix. One hundred and thirty one cervical specimens, consisting of normal cervix (n = 43), cervical intraepithelial neoplasia (CIN) lesions (n = 40) [16 LSIL: CIN 1 and 24 HSIL: 9 CIN 2 and 15 CIN 3] and cervical squamous cell carcinomas (n = 48) [16 SCC I, 17 SCC II, 7 SCC III and 8 SCC IV] were examined immunohistochemically in paraffin sections. All samples of the normal cervix were negative for p16. Immunoreactivity of p16 was observed in 4/ 16 LSIL, 12/24 HSIL and 30/48 SCC. In all p16-positive samples, both nuclear and cytoplasmic staining were observed. High expression of p16 (> 50 % of cell stained) was found in HSIL and SCC. Ki-67 index was significantly (p < 0.05) higher in high-grade squamous intraepithelial lesions (HSIL: CIN 2 & 3) and SCC lesions when compared to normal cervices. The expression of p16 and Ki-67 proliferation profile ( 30 % stained cells) were significantly associated with the grade of lesions (χ2 = 6.832, p = 0.033 and χ2 = 10.952; p = 0.012 respectively). There was no significant relationship demonstrated between p16 positivity and Ki-67 proliferation profile (χ2 = 0.292; p = 0.589). Our results indicated that p16protein may be involved in the carcinogenesis of cervical cancer. However, overexpression of p16 seemed to have no effect on cell proliferation. The expression of p16 and pKi-67 may be useful in cases where it is difficult to make a diagnosis by histology

DOES PALM OIL VITAMIN E REDUCE THE RISK OF PREGNANCY INDUCED HYPERTENSION?

In view of the high anti-oxidative potential of tocotrienol, the role of the tocotrienol-rich fraction (TRF) of palm oil in preventing pregnancy induced hypertension (PIH) was explored in a randomized double-blind placebo-controlled clinical trial in an urban teaching hospital. Healthy primigravidae were randomized to receive either oral TRF 100mg daily or placebo, from early second trimester until delivery. Out of 299 women, 151 were randomized into the TRF arm and 148 into the placebo arm. A total of 15 (5.0%) developed PIH. Although there was no statistically significant difference in the incidence of PIH (4/151 or 2.6% in the TRF arm vs 11/148 or 7.4% in the placebo arm, p = 0.058) between the two arms, there was a tendency towards a lower incidence of PIH in the TRF arm compared to the placebo arm. With TRF supplementation, the relative risk (RR) of PIH was 0.36 (95% CI 0.12–1.09). In conclusion, although TRF from palm oil does not statistically significantly reduce the risk of development of PIH in the population studied, the 64% reduction in incidence of PIH is substantial. The findings warrant further clinical trials, particularly in high risk populations

Image_2_Targeted Next-Generation Sequencing Identifies Actionable Targets in Estrogen Receptor Positive and Estrogen Receptor Negative Endometriod Endometrial Cancer.tif

<p>Endometrioid endometrial cancer (EEC) is the commonest form of endometrial cancer and can be divided into estrogen receptor (ER) positive and negative subtypes. The mutational profiles of EEC have been shown to aid in tailoring treatment; however, little is known about the differences between the gene mutation profiles between these two subtypes. This study aims to investigate the gene mutation profile in ER positive and negative EEC, and to further elucidate the role of WHSC1 mutations in this cancer. EEC and normal endometrial tissues were obtained from 29 patients and subjected to next-generation sequencing (NGS) using Ion Ampliseq Comprehensive Cancer Panel^TM targeting 409 cancer related. A total of 741 non-synonymous alterations were identified from 272 genes in ER positive subtype while 448 non-synonymous variants were identified from 221 genes in ER negative subtype. PTEN is the most frequently altered gene in ER positive subtype (64%, 7/11) while ARID1A is the most frequently altered gene in ER negative subtype (50%, 4/8). We also identified alterations in ERRB3 (36%, 4/11), GNAS (36%, 4/11), and WHSC1 (27%, 3/11) in the ER positive subtype. WHSC1 R1126H and L1268P were shown to significantly increase cell viability, proliferation, migration, and survival. In addition, reduction in ER expression sensitized EEC-1 cell with WHSC1 L1268P mutant to Fulvestrant treatment. We revealed the mutational spectra of ER positive and ER negative EEC that could lead to better understanding of the biological mechanisms of endometrial cancer and may ultimately result in improvement of treatment options and patient prognosis.</p

Data_Sheet_1_Targeted Next-Generation Sequencing Identifies Actionable Targets in Estrogen Receptor Positive and Estrogen Receptor Negative Endometriod Endometrial Cancer.xls

<p>Endometrioid endometrial cancer (EEC) is the commonest form of endometrial cancer and can be divided into estrogen receptor (ER) positive and negative subtypes. The mutational profiles of EEC have been shown to aid in tailoring treatment; however, little is known about the differences between the gene mutation profiles between these two subtypes. This study aims to investigate the gene mutation profile in ER positive and negative EEC, and to further elucidate the role of WHSC1 mutations in this cancer. EEC and normal endometrial tissues were obtained from 29 patients and subjected to next-generation sequencing (NGS) using Ion Ampliseq Comprehensive Cancer Panel^TM targeting 409 cancer related. A total of 741 non-synonymous alterations were identified from 272 genes in ER positive subtype while 448 non-synonymous variants were identified from 221 genes in ER negative subtype. PTEN is the most frequently altered gene in ER positive subtype (64%, 7/11) while ARID1A is the most frequently altered gene in ER negative subtype (50%, 4/8). We also identified alterations in ERRB3 (36%, 4/11), GNAS (36%, 4/11), and WHSC1 (27%, 3/11) in the ER positive subtype. WHSC1 R1126H and L1268P were shown to significantly increase cell viability, proliferation, migration, and survival. In addition, reduction in ER expression sensitized EEC-1 cell with WHSC1 L1268P mutant to Fulvestrant treatment. We revealed the mutational spectra of ER positive and ER negative EEC that could lead to better understanding of the biological mechanisms of endometrial cancer and may ultimately result in improvement of treatment options and patient prognosis.</p

Image_1_Targeted Next-Generation Sequencing Identifies Actionable Targets in Estrogen Receptor Positive and Estrogen Receptor Negative Endometriod Endometrial Cancer.tif

<p>Endometrioid endometrial cancer (EEC) is the commonest form of endometrial cancer and can be divided into estrogen receptor (ER) positive and negative subtypes. The mutational profiles of EEC have been shown to aid in tailoring treatment; however, little is known about the differences between the gene mutation profiles between these two subtypes. This study aims to investigate the gene mutation profile in ER positive and negative EEC, and to further elucidate the role of WHSC1 mutations in this cancer. EEC and normal endometrial tissues were obtained from 29 patients and subjected to next-generation sequencing (NGS) using Ion Ampliseq Comprehensive Cancer Panel^TM targeting 409 cancer related. A total of 741 non-synonymous alterations were identified from 272 genes in ER positive subtype while 448 non-synonymous variants were identified from 221 genes in ER negative subtype. PTEN is the most frequently altered gene in ER positive subtype (64%, 7/11) while ARID1A is the most frequently altered gene in ER negative subtype (50%, 4/8). We also identified alterations in ERRB3 (36%, 4/11), GNAS (36%, 4/11), and WHSC1 (27%, 3/11) in the ER positive subtype. WHSC1 R1126H and L1268P were shown to significantly increase cell viability, proliferation, migration, and survival. In addition, reduction in ER expression sensitized EEC-1 cell with WHSC1 L1268P mutant to Fulvestrant treatment. We revealed the mutational spectra of ER positive and ER negative EEC that could lead to better understanding of the biological mechanisms of endometrial cancer and may ultimately result in improvement of treatment options and patient prognosis.</p