Authors: Xin Zhao, Han Li, Shaocheng Lyu...

Pancreatic adenosquamous carcinoma (PASC) - a rare pathological pancreatic cancer (PC) type - has a poor prognosis due to high malignancy. To examine the heterogeneity of PASC, we performed single-cell RNA sequencing (scRNA-seq) profiling with sample tissues from a healthy donor pancreas, an intraductal papillary mucinous neoplasm, and a patient with PASC. Of 9,887 individual cells, ten cell subpopulations were identified, including myeloid, immune, ductal, fibroblast, acinar, stellate, endothelial, and cancer cells. Cancer cells were divided into five clusters. Notably, cluster 1 exhibited stem-like phenotypes expressing UBE2C, ASPM, and TOP2A. We found that S100A2 is a potential biomarker for cancer cells. LGALS1, NPM1, RACK1, and PERP were upregulated from ductal to cancer cells. Furthermore, the copy number variations in ductal and cancer cells were greater than in the reference cells. The expression of EREG, FCGR2A, CCL4L2, and CTSC increased in myeloid cells from the normal pancreas to PASC. The gene sets expressed by cancer-associated fibroblasts were enriched in the immunosuppressive pathways. We demonstrate that EGFR-associated ligand-receptor pairs are activated in ductal-stromal cell communications. Hence, this study revealed the heterogeneous variations of ductal and stromal cells, defined cancer-associated signaling pathways, and deciphered intercellular interactions following PASC progression.

Topics: Adenocarcinoma, Mucinous; Biomarkers, Tumor; Carcinoma, Adenosquamous; Chemotactic Factors; DNA Copy Number Variations; ErbB Receptors; Genetic Heterogeneity; Humans; Neoplasm Proteins; Pancreatic Neoplasms; S100 Proteins; Sequence Analysis, RNA; Single-Cell Analysis; Transcriptome

PubMed: 34326696
DOI: 10.7150/ijbs.58886

Review

Authors: Yin-Yin Chen, Anna Fen-Yau Li, Kuo-Hung Huang...

Adenosquamous carcinoma of the stomach is a very rare disease, consisting of less than 0.4 % of all stomach cancer. From 1991 to 2013, a total of 2800 patients received gastrectomy for gastric cancer at Taipei Veterans General hospital. Among them, seven patients (0.25 %) diagnosed as adenosquamous carcinoma were enrolled. The clinicopathologic characteristics and prognosis were analyzed. The mean age of the seven patients was 62.3 years-old. There were 5 males and 2 females. Six patients were stage III disease and one patient was stage IV disease. Four patients finally died of gastric cancer. Only one patient had no recurrence until death. Among the seven patients, adenocarcinoma component comprises the majority of the metastatic lymph node in 6 patients (85.7 %). The only one patient with major squamous cell carcinoma component in metastatic lymph node had no tumor recurrence till death. Adenosquamous carcinoma of stomach is a rare disease and is associated with a poor prognosis. The component of adenocarcinoma and squamous cell carcinoma in the metastatic lymph node may influence the prognosis.

Topics: Adenocarcinoma; Aged; Carcinoma, Adenosquamous; Carcinoma, Squamous Cell; Female; Follow-Up Studies; Humans; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Prognosis; Stomach Neoplasms

PubMed: 25567665
DOI: 10.1007/s12253-014-9890-7

Authors: Valerie A White, Martin D Hyrcza, Jochen K Lennerz...

Mucoepidermoid carcinoma (MEC) and adenosquamous carcinoma (ASC) have overlapping histopathological appearances and sites of occurrence, which may cause diagnostic difficulty impacting subsequent treatment. We conducted a systematic review of the scientific literature to determine whether molecular alterations were sufficiently different in MEC and ASC to aid in classifying the two entities. We searched Medline, Embase and Web of Science for studies reporting molecular determinations of ASC and/or MEC and screened retrieved records for eligibility. Two independent researchers reviewed included studies, assessed methodological quality and extracted data. Of 8623 identified records, 128 articles were included for analysis: 5 which compared the two tumors in the same investigation using the same methods and 123 which examined the tumors separately. All articles, except one were case series of moderate to poor methodological quality. The 5 publications examining both tumors showed that 52/88 (59%) MEC and 0% of 110 ASC had rearrangement of the MAML2 gene as detected by FISH and/or RT-PCR, but did not investigate other genes. In the entire series MEC had MAML2 gene rearrangement in 1337/2009 (66.6%) of tumors studied. The articles examining tumors separately found that MEC had mutations in EGFR (11/329 cases, 3.3%), KRAS (11/266, 4.1%) and ERBB2 (9/126, 7.1%) compared with ASC that had mutations in EGFR (660/1705, 38.7%), KRAS (143/625, 22.9%) and ERBB2 (6/196, 3.1%). The highest level of recurrent mutations was in pancreatic ASC where (108/126, 85.7%) reported mutations in KRAS. The EGFR mutations in ASC were similar in number and kind to those in lung adenocarcinoma. By standards of systematic review methodology and despite the large number of retrieved studies, we did not find adequate evidence for a distinctive molecular profile of either MEC or ASC that could definitively aid in its classification, especially in histologically difficult cases that are negative for MAML2 rearrangement. The case series included in this review indicate the relevance of MAML2 rearrangement to support the diagnosis of MEC, findings that should be confirmed by additional research with adequate study design.

Topics: Carcinoma, Adenosquamous; Carcinoma, Mucoepidermoid; DNA-Binding Proteins; ErbB Receptors; Humans; In Situ Hybridization, Fluorescence; Nuclear Proteins; Proto-Oncogene Proteins p21(ras); Salivary Gland Neoplasms; Trans-Activators; Transcription Factors

PubMed: 35871081
DOI: 10.1038/s41379-022-01100-z

Authors: Yuqiang Du, Hongkun Tian, Zhiliang Chen...

Primary gastric adenosquamous carcinoma (PGASC) is a rare type of gastric cancer with limited research and poorly understood clinicopathological features. This study investigated the clinicopathological features and outcomes of PGASC. Patients with PGASC from Union Hospital, Tongji Medical College, Huazhong University of Science and Technology and from the published literature were enrolled in this study. Survival curves were generated using the Kaplan-Meier method, and prognostic factors were identified through Cox proportional hazards regression models. This study identified 76 eligible cases of PGASC, with 45 cases from published literature and 31 from our center. The most prevalent symptoms were abdominal pain and dysphagia, with a median age of 62 years (range: 29-84 years). The primary lesions were predominantly in the proximal stomach, with a median tumor size of 6.5 cm (range: 1.5-16.0 cm). Tumor stages II, III, and IV were detected in 12 (16.7%), 43 (59.7%), and 17 (23.6%) patients, respectively. Most tumors were poorly differentiated in both the squamous cell carcinoma (SCC) component and adenocarcinoma (AC) component. The median survival time was 17 months (range: 2-122 months). The 1, 3, and 5-year overall survival (OS) was 60.7%, 31.1%, and 24.1%, respectively. Multivariate analysis revealed that OS was independently predicted by the proportion of SCC component, differentiation of AC component, and tumor stage. PGASC is a rare disease with a poor prognosis. A high proportion of SCC components, low differentiated AC components, and advanced tumor were associated with worse survival in patients with PGASC. Adjuvant therapy did not improve survival time.

Topics: Humans; Stomach Neoplasms; Middle Aged; Male; Carcinoma, Adenosquamous; Female; Aged; Adult; Aged, 80 and over; Prognosis; Neoplasm Staging; Kaplan-Meier Estimate

PubMed: 39003328
DOI: 10.1038/s41598-024-66701-x

Authors: Zhihao Huang, Jiakun Wang, Rongguiyi Zhang...

BACKGROUND

The incidence and mortality of pancreatic adenosquamous carcinoma (PASC) have received little attention. The goal of our study was to explore the overall epidemiological trend of PASC at the population level.

METHODS

The Surveillance, Epidemiology, and End Results database was used to collect the incidence, incidence-based (IB) mortality, and patient details for PASC from 2000 to 2017. The Joinpoint regression tool was used to examine the trends in incidence and IB mortality. The Kaplan-Meier approach was used for survival analysis. Univariate and multivariate Cox regression analyses were used to determine the independent prognostic factors.

RESULTS

We included 815 patients with PASC in the study. The incidence of PASC continuously increased from 2000 to 2017, with an annual percentage change (APC) of 3.9% (95% CI: 2.2%-5.7%, p < 0.05). IB mortality also increased continuously, with an APC of 5.0% (95% CI: 2.5%-7.6%, p < 0.05). Multivariate Cox regression analysis revealed that age, treatment, regional lymph node involvement, and tumor size were independent prognostic factors. Nomograms were created for PASC to predict 1- and 2-year survival probabilities, respectively.

CONCLUSIONS

The incidence and IB mortality of PASC had a sustained and rapid increase, indicating that the preventive and treatment measures for PASC were not ideal. We must identify the significance of this condition as soon as possible, and commit greater attention and resources to PASC research.

Topics: Humans; Carcinoma, Adenosquamous; Prognosis; Nomograms; Pancreatic Neoplasms; SEER Program

PubMed: 36850060
DOI: 10.1002/cam4.5700

Review

Authors: Simona Stolnicu, Lynn Hoang, Qin Zhou...

Although both the 2014 and 2020 World Health Organization (WHO) criteria require unequivocal glandular and squamous differentiation for a diagnosis of cervical adenosquamous carcinoma (ASC), in practice, ASC diagnoses are often made in tumors that lack unequivocal squamous and/or glandular differentiation. Considering the ambiguous etiologic, morphologic, and clinical features and outcomes associated with ASCs, we sought to redefine these tumors. We reviewed slides from 59 initially diagnosed ASCs (including glassy cell carcinoma and related lesions) to confirm an ASC diagnosis only in the presence of unequivocal malignant glandular and squamous differentiation. Select cases underwent immunohistochemical profiling as well as human papillomavirus (HPV) testing by in situ hybridization. Of the 59 cases originally classified as ASCs, 34 retained their ASC diagnosis, 9 were reclassified as pure invasive stratified mucin-producing carcinomas, 10 as invasive stratified mucin-producing carcinomas with other components (such as HPV-associated mucinous, usual-type, or ASCs), and 4 as HPV-associated usual or mucinous adenocarcinomas with benign-appearing squamous metaplasia. Two glassy adenocarcinomas were reclassified as poorly differentiated HPV-associated carcinomas based on morphology and immunophenotype. There were no significant immunophenotypic differences between ASCs and pure invasive stratified mucin-producing carcinomas with regard to HPV and other markers including p16 expression. Although limited by a small sample size, survival outcomes seemed to be similar between all groups. ASCs should be diagnosed only in the presence of unequivocal malignant glandular and squamous differentiation. The 2 putative glassy cell carcinomas studied did not meet our criteria for ASC and categorizing them as such should be reconsidered.

Topics: Female; Humans; Carcinoma, Adenosquamous; Papillomavirus Infections; Uterine Cervical Neoplasms; Adenocarcinoma; Carcinoma, Squamous Cell; Mucins

PubMed: 36044310
DOI: 10.1097/PGP.0000000000000921

Authors: Alexander Melamed, Daniel J Margul, Ling Chen...

BACKGROUND

Minimally invasive surgery was adopted as an alternative to laparotomy (open surgery) for radical hysterectomy in patients with early-stage cervical cancer before high-quality evidence regarding its effect on survival was available. We sought to determine the effect of minimally invasive surgery on all-cause mortality among women undergoing radical hysterectomy for cervical cancer.

METHODS

We performed a cohort study involving women who underwent radical hysterectomy for stage IA2 or IB1 cervical cancer during the 2010-2013 period at Commission on Cancer-accredited hospitals in the United States. The study used inverse probability of treatment propensity-score weighting. We also conducted an interrupted time-series analysis involving women who underwent radical hysterectomy for cervical cancer during the 2000-2010 period, using the Surveillance, Epidemiology, and End Results program database.

RESULTS

In the primary analysis, 1225 of 2461 women (49.8%) underwent minimally invasive surgery. Women treated with minimally invasive surgery were more often white, privately insured, and from ZIP Codes with higher socioeconomic status, had smaller, lower-grade tumors, and were more likely to have received a diagnosis later in the study period than women who underwent open surgery. Over a median follow-up of 45 months, the 4-year mortality was 9.1% among women who underwent minimally invasive surgery and 5.3% among those who underwent open surgery (hazard ratio, 1.65; 95% confidence interval [CI], 1.22 to 2.22; P=0.002 by the log-rank test). Before the adoption of minimally invasive radical hysterectomy (i.e., in the 2000-2006 period), the 4-year relative survival rate among women who underwent radical hysterectomy for cervical cancer remained stable (annual percentage change, 0.3%; 95% CI, -0.1 to 0.6). The adoption of minimally invasive surgery coincided with a decline in the 4-year relative survival rate of 0.8% (95% CI, 0.3 to 1.4) per year after 2006 (P=0.01 for change of trend).

CONCLUSIONS

In an epidemiologic study, minimally invasive radical hysterectomy was associated with shorter overall survival than open surgery among women with stage IA2 or IB1 cervical carcinoma. (Funded by the National Cancer Institute and others.).

Topics: Adenocarcinoma; Adult; Carcinoma, Adenosquamous; Carcinoma, Squamous Cell; Cause of Death; Chi-Square Distribution; Cohort Studies; Female; Humans; Hysterectomy; Middle Aged; Minimally Invasive Surgical Procedures; Neoplasm Recurrence, Local; Neoplasm Staging; Propensity Score; SEER Program; Survival Analysis; Survival Rate; Uterine Cervical Neoplasms

PubMed: 30379613
DOI: 10.1056/NEJMoa1804923

Review

Authors: Maitham A Moslim, Max D Lefton, Eric A Ross...

BACKGROUND

Adenosquamous carcinoma (ASC) of the pancreas is a rare form of malignancy with a poor prognosis. We herein report our case series with review of the contemporary literature.

METHODS

With institutional review board approval, we identified 23 patients with pancreatic ASC.

RESULTS

ASC was more common in women (61%), with a median age of 73 y at presentation. The tumor was in the head of the pancreas in 65% of cases. Six cases (26%) had resectable disease, three (13%) were borderline resectable, and eight (34.7%) were locally advanced or metastatic. First-line treatment included pancreatic resection in eight cases (34.8%), concurrent neoadjuvant chemoradiation in three (13%), and neoadjuvant chemotherapy in two (8.7%). Most resected tumors had pathological T3 stage (80%). Pathological nodal disease was demonstrated in 60%, and margins were positive in three cases. Complete pathological response was not observed, although fibrosis presented in only one case (10%). Eventually, twenty patients developed metastatic disease. Overall survival is 11.5 [95% confidence interval 6, 14.5] months.

CONCLUSIONS

ASC demonstrates a more aggressive malignant phenotype and carries a worse prognosis. Oncological resection is the mainstay of treatment. Neoadjuvant chemoradiation is an emerging approach in the management of ASC that has been extrapolated from the adenocarcinoma neoadjuvant trials.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Adenosquamous; Chemoradiotherapy, Adjuvant; Chemotherapy, Adjuvant; Disease-Free Survival; Female; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Neoplasm Staging; Pancreas; Pancreatectomy; Pancreatic Neoplasms; Practice Guidelines as Topic; Prognosis; Tomography, X-Ray Computed; Treatment Outcome

PubMed: 33190924
DOI: 10.1016/j.jss.2020.09.024

Randomized Controlled Trial

Authors: D Lorusso, N Colombo, C Dubot...

BACKGROUND

In KEYNOTE-826 (NCT03635567), pembrolizumab plus chemotherapy (±bevacizumab) significantly improved overall survival (OS) and progression-free survival (PFS) in patients with persistent, recurrent, or metastatic cervical cancer. This exploratory analysis examined outcomes in patient subgroups defined by bevacizumab use.

PATIENTS AND METHODS

Eligible adult patients had persistent, recurrent, or metastatic squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix not previously treated with chemotherapy and not amenable to curative treatment; measurable disease per RECIST v1.1; and an Eastern Cooperative Oncology Group performance status ≤1. Patients were randomly allocated 1 : 1 to pembrolizumab 200 mg every 3 weeks or placebo for up to 35 cycles plus chemotherapy (±bevacizumab 15 mg/kg). Dual primary endpoints were OS and PFS per RECIST v1.1 by investigator assessment. Outcomes were assessed in subgroups defined by bevacizumab use. Hazard ratios (HRs) and 95% confidence intervals (CIs) were based on a stratified Cox regression model.

RESULTS

A total of 617 patients were randomly assigned [pembrolizumab arm, n = 308 (63.6% with bevacizumab); placebo arm, n = 309 (62.5% with bevacizumab)]. The most common reason for bevacizumab exclusion was medical contraindication (75.9%). Among patients who received bevacizumab, HRs (95% CIs) for PFS favored the pembrolizumab arm in the programmed cell death-ligand 1 combined positive score ≥1 [0.56 (0.43-0.73)] and all-comer [0.57 (0.45-0.73)] populations; OS results were 0.60 (0.45-0.79) and 0.61 (0.47-0.80), respectively. Among patients who did not receive bevacizumab, HRs (95% CIs) for PFS also favored the pembrolizumab arm in the programmed cell death-ligand 1 combined positive score ≥1 [0.61 (0.44-0.85)] and all-comer [0.69 (0.50-0.94)] populations; OS results were 0.61 (0.44-0.85) and 0.67 (0.49-0.91), respectively. Among patients who received bevacizumab, grade ≥3 treatment-related adverse events occurred in 74.0% of patients in the pembrolizumab arm and 66.8% in the placebo arm.

CONCLUSION

Pembrolizumab plus chemotherapy prolonged PFS and OS and had manageable safety compared with placebo plus chemotherapy in patient subgroups defined by bevacizumab use.

Topics: Humans; Female; Bevacizumab; Antibodies, Monoclonal, Humanized; Uterine Cervical Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Middle Aged; Adult; Neoplasm Recurrence, Local; Aged; Progression-Free Survival; Carcinoma, Squamous Cell; Adenocarcinoma; Carcinoma, Adenosquamous; Double-Blind Method

PubMed: 39393777
DOI: 10.1016/j.annonc.2024.10.002

Authors: Jacob T Polaski, Dylan B Udy, Luisa F Escobar-Hoyos...

Pancreatic adenosquamous carcinoma (PASC) is an aggressive cancer whose mutational origins are poorly understood. An early study reported high-frequency somatic mutations affecting UPF1, a nonsense-mediated mRNA decay (NMD) factor, in PASC, but subsequent studies did not observe these lesions. The corresponding controversy about whether mutations are important contributors to PASC has been exacerbated by a paucity of functional studies. Here, we modeled two mutations in human and mouse cells to find no significant effects on pancreatic cancer growth, acquisition of adenosquamous features, splicing, UPF1 protein, or NMD efficiency. We subsequently discovered that 45% of mutations reportedly present in PASCs are identical to standing genetic variants in the human population, suggesting that they may be non-pathogenic inherited variants rather than pathogenic mutations. Our data suggest that is not a common functional driver of PASC and motivate further attempts to understand the genetic origins of these malignancies.

Topics: Animals; Carcinoma, Adenosquamous; Genetic Variation; Humans; Mice; Pancreatic Neoplasms; RNA Helicases; Trans-Activators

PubMed: 33404013
DOI: 10.7554/eLife.62209