Managing facial infiltrating lipomatosis associated with PIK3CA mutation:From surgery to targeted therapy

Facial infiltrating lipomatosis(FIL)is a congenital asymmetrical deformity of the maxillofacial region that can significantly affect a patient’s facial appearance and function.With the development of sequencing technologies,PIK3CA mutations are considered among the potential etiologies of FIL.The management and treatment of FIL involves plastic surgery;more recently,an improved understanding of its pathogenesis has given rise to new treatment options,including targeted therapy.Here we report the clinical data of two patients diagnosed with FIL and present current curative concepts.

PIK3CA gene mutations in Northwest Chinese esophageal squamous cell carcinoma

AIM To evaluate PIK3 CA gene mutational status in Northwest Chinese esophageal squamous cell carcinoma(ESCC) patients, and examine the associations of PIK3 CA gene mutations with clinicopathological characteristics and clinical outcome.METHODS A total of 210 patients with ESCC who underwent curative resection were enrolled in this study. Pyrosequencing was applied to investigate mutations in exons 9 and 20 of PIK3 CA gene in 210 Northwest Chinese ESCCs. The associations of PIK3 CA gene mutations with clinicopathological characteristics and clinical outcome were examined.RESULTS PIK3 CA gene mutations in exon 9 were detected in 48 cases(22.9%) of a non-biased database of 210 curatively resected Northwest Chinese ESCCs. PIK3 CA gene mutations were not associated with sex, tobacco use, alcohol use, tumor location, stage, or local recurrence. When compared with wild-type PIK3 CA gene cases, patients with PIK3 CA gene mutations in exons 9 experienced significantly better disease-free survival and overall survival rates.CONCLUSION The results of this study suggest that PIK3 CA gene mutations could act as a prognostic biomarker in Northwest Chinese ESCC patients.

PIK3CA mutation in Chinese patients with lung squamous cell carcinoma

Objective： To investigate PIK3CA mutation in Chinese patients with lung squamous cell carcinoma （LSCC） and explore their relationship with clinicopathological profiles. Methods： Tumor samples from 123 cases of LSCC were included in this study. PIK3CA mutations in exon 9 and 20 were screened by pyrosequencing and confirmed by clone sequencing or amplification refractory mutation system （ARMS）. Denaturing performance liquid chromatography （DHPLC） was employed for evaluation of EGFR mutation in exon 19, 21 and KRAS mutation. Results： PIK3CA mutations were found in 3 （2.4%） patients. The mutation type included E545K, E452Q and H1047R. Of these three patients, one coupled with EGFR mutation, and the other two coupled with PIK3CA amplification. All the three patients shared the same clinicopathologic characteristics： male, less than 60 years old, had smoke history, stage III and carried wild-type KRAS. Conclusions： The frequency of PIK3CA mutation is low in Chinese patients with LSCC. The mutational status of PIK3CA is not mutually exclusive to EGFR mutation.

PIK3CA mutation in non-metastatic triple-negative breast cancer as a potential biomarker of early relapse:A case report

BACKGROUND Currently,the detection of PIK3CA mutations is of special interest in personalized medicine because it is frequently found in triple-negative breast cancer(TNBC).The PI3KCA mutation is an independent negative prognostic factor for survival in metastatic breast cancer,and its prognostic value in liquid biopsy as a biomarker of treatment and early relapse is under investigation,both for metastatic disease and neoadjuvant scenario with curative intent.CASE SUMMARY A 54-year-old female patient with TNBC clinical stage IIIA,who,after receiving neoadjuvant chemotherapy(based on anthracyclines and taxanes),surgery,radiotherapy,and adjuvant capecitabine,was detected with a PI3KCA mutation in tissue and peripheral blood(ctDNA in liquid biopsy).After 10 mo,the patient had disease relapse of left cervical node disease.CONCLUSION The detection of PIK3CA mutation in TNBC after neoadjuvant treatment might be associated with early relapse or rapid disease progression.

Long-term survival of a patient with pancreatic cancer and lung metastasis:A case report and review of literature

BACKGROUND Pancreatic cancer(PC)is a leading cause of cancer-related death,given its poor prognosis and the limited benefits of traditional therapies.As tumors become more genetically disorganized as they progress,genetic mutations might become new markers for us to predict their behavior.Nowadays,many inhibitors can selectively target gene products as a form of targeted therapy,with some showing promise as treatment for various types of cancer.CASE SUMMARY We describe a rare case of a PC patient with long-term survival of more than 8 yr.The patient was diagnosed with pancreatic ductal adenocarcinoma(PDAC)with BAP1 and PIK3CA gene mutations and Raf1 fusion and achieved partial response twice after treatment with apatinib in combination with chemotherapy.CONCLUSION BAP1,PIK3CA mutations,and Raf1 fusion are rare in PDAC.Patients with these three gene alterations of PDAC may achieve long-term survival with apatinib.Further research in other contexts is needed to determine whether apatinib has ideal efficacy for PC treatment.

A biomarker study in Peruvian males with breast cancer

BACKGROUND Breast cancer(BC)frequency in males is extremely low and tumor features vary from its female counterpart.Breast cancer clinical and pathological features differ by race in women.Tumor infiltrating lymphocyte(TIL)levels,mismatch repair(MMR)protein loss,androgen receptor(AR)expression,and PIK3CA gene mutations are predictive biomarkers of response to biological therapy in female BC.There is limited information about clinical and pathological features as well as predictive biomarkers in males of non-Caucasian races with BC.AIM To investigate clinicopathological features and biomarkers of BC tumors in males and their prognostic value in Peruvian population.METHODS This study looked at a single-institution series of 54 Peruvian males with invasive BC who were diagnosed from Jan 2004 to June 2018.Standard pathological features,TIL levels,MMR proteins,AR immunohistochemistry staining,and PIK3CA gene mutations were prospectively evaluated in cases with available paraffin material.Percentage of AR and estrogen receptor(ER)positive cells was additionally calculated by software after slide scanning.Statistical analyses included association tests,intraclass correlation test and Kaplan Meier overall survival curves.RESULTS The median age was 63 years and most cases were ER-positive(85.7%),HER2 negative(87.2%),Luminal-A phenotype(60%)and clinical stage II(41.5%)among our male breast tumors.Median TIL was 10%and higher levels tended to be associated with Luminal-B phenotype and higher grade.AR-positive was found in 85.3%and was correlated with ER(intraclass index of 0.835,P<0.001).Loss of MMR proteins was found in 15.4%and PIK3CA mutation(H1047R)in 14.3%(belonged to the Luminal-A phenotype).Loss of MMR proteins was associated with AR-negative(P=0.018)but not with ER(P=0.43)or TIL(P=0.84).Early stages(P<0.001)and lower grade(P=0.006)were associated with longer overall survival.ER status,phenotype,AR status,TIL level,MMR protein loss nor PIK3CA mutation was not associated with survival(P>0.05).CONCLUSION Male BC is usually ER and AR positive,and Luminal-A.MMR loss and PIK3CA mutations are infrequent.Stage and grade predicted overall survival in our South American country population.

Network Analysis Reveals A Signaling RegulatoryLoop in PIK3CA-mutated Breast Cancer Predicting Survival Outcome

Mutated genes are rarely common even in the same pathological type between cancer patients and as such, it has been very challenging to interpret genome sequencing data and difficult to predict clinical outcomes. PIK3 CA is one of a few genes whose mutations are relatively popular in tumors. For example, more than 46.6% of luminal-A breast cancer samples have PIK3 CA mutated, whereas only 35.5% of all breast cancer samples contain PIK3 CA mutations. To understand the function of PIK3 CA mutations in luminal A breast cancer, we applied our recentlyproposed Cancer Hallmark Network Framework to investigate the network motifs in the PIK3CA-mutated luminal A tumors. We found that more than 70% of the PIK3CA-mutated luminal A tumors contain a positive regulatory loop where a master regulator(PDGF-D), a second regulator(FLT1) and an output node(SHC1) work together. Importantly, we found the luminal A breast cancer patients harboring the PIK3 CA mutation and this positive regulatory loop in their tumors have significantly longer survival than those harboring PIK3 CA mutation only in their tumors. These findings suggest that the underlying molecular mechanism of PIK3 CA mutations in luminal A patients can participate in a positive regulatory loop, and furthermore the positive regulatory loop(PDGF-D/FLT1/SHC1) has a predictive power for the survival of the PIK3 CAmutated luminal A patients.